2124-57-4

Basic information

• Product Name: Vitamin K2(35)
• Synonyms: MENAQUINONE-7;(all-E)-2-(3,7,11,15,19,23,27-Heptamethyl-2,6,10,14,18,22,26-octacosaheptaenyl)-3-methyl-1,4-naphthalenedione;Menaquinone K7;Vitamin K2(35);Vitamin MK 7;Menlaquinone 7;MK-7;2-[(2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-Heptamethyl-2,6,10,14,18,22,26-octacosaheptenyl]-3-methyl-1,4-naphthalenedione
• CAS NO: 2124-57-4
• Molecular Formula: C₄₆H₆₄O₂
• Molecular Weight: 649
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics
• Mol File: 2124-57-4.mol
• Article Data: 8

Chemical Properties

• Melting Point: 54 °C
• Boiling Point: bp0.0002 200° (some dec)
• Flash Point: 254.9 °C
• Appearance: /
• Density: 0.961
• Vapor Pressure: 1.38E-20mmHg at 25°C
• Refractive Index: 1.532
• Storage Temp.: -20°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• Stability: Light and Temperature Sensitive
• CAS DataBase Reference: Vitamin K2(35)(CAS DataBase Reference)
• NIST Chemistry Reference: Vitamin K2(35)(2124-57-4)
• EPA Substance Registry System: Vitamin K2(35)(2124-57-4)

Safety Data

• Hazardous Substances Data: 2124-57-4(Hazardous Substances Data)

Usage

Description

Menaquinone 7 (MK-7) is a vitamin K2 analog that has been found in a variety of fermented foods. It increases osteocalcin, osteoprotegerin, and RANKL mRNA expression in osteoblastic MC3T3E cells. MK-7 (1 μM) increases alkaline phosphatase activity and calcium content in femoral-metaphyseal tissues isolated from normal and skeletal-unloaded rats. In vivo, MK-7 (100 μg/g diet) inhibits aortic and myocardial calcification and decreases aortic alkaline phosphatase tissue concentrations in a rat model of extraosseous calcification. It also increases trabecular number, bone mineral density, and bone mineral content in a rat model of ovariectomy-induced bone loss.

Chemical Properties

Light Yellow Crystalline Solid

Uses

Different sources of media describe the Uses of 2124-57-4 differently. You can refer to the following data:
1. Vitamin (prothrombogenic)
2. Menaquinones are isoprenoid quinones of the naphthalene series and belongs to the K2 Vitamin homologs. Menaquinones were originally discovered as the anti-hemorrhagic factor and now encompasses a vari ety of physiological processes. Menaquinone 7 belongs to the class of K2-Vitamins homologs. Menaquinone 7 has been identified as the most bioactive cofactor for the carboxylation reaction of Gla-prote ins such as osteocalcin and matrix-Gla protein, which plays a crucial role in building and maintaining overall bone health.
3. Vitamin K2 (MK-7)-(5,6,7,8-d4,2-methyl-d3) can be used as a stable isotope internal standard for data interpretation in specific biological samples.

Definition

ChEBI: A menaquinone whose side-chain contains seven isoprene units in an all-trans-configutation.

General Description

Vitamin K2, also known as menaquinone, is a polyisoprenoid-substituted?napthoquinone. Menaquinone-7 (MK-7) is a subtype of vitamin K2. It is found in animals, soy protein, fermented products and is primarily produced by bacteria.Vitamin K2 (MK-7)-(5,6,7,8-d4,2-methyl-d3) is a deuterated vitamin K2 wherein C-5, C-6, C-7, C-8, and 2-methyl protons are replaced by deuterium.

InChI:InChI=1/C46H64O2/c1-34(2)18-12-19-35(3)20-13-21-36(4)22-14-23-37(5)24-15-25-38(6)26-16-27-39(7)28-17-29-40(8)32-33-42-41(9)45(47)43-30-10-11-31-44(43)46(42)48/h10-11,18,20,22,24,26,28,30-32H,12-17,19,21,23,25,27,29,33H2,1-9H3/b35-20+,36-22+,37-24+,38-26+,39-28+,40-32+

Synthetic route

2-(3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaenyl)-1,4-dimethoxy-3-methylnaphthalene (1218784-62-3) → menaquinone-7 (2124-57-4)

Conditions	Yield
With ammonium cerium (IV) nitrate In water; acetonitrile at 20℃; for 4.08333h;	80%
With ammonium cerium (IV) nitrate In acetonitrile at 20℃; for 4.08333h;	80%
With ammonium cerium (IV) nitrate In water; acetonitrile at 0℃; for 0.75h;	72%
With ammonium cerium (IV) nitrate In dichloromethane; water; acetonitrile at 0℃; for 0.75h;	0.753 g

C50H74O2 (1597486-88-8) → menaquinone-7 (2124-57-4)

Conditions	Yield
With ammonium cerium (IV) nitrate In dichloromethane; water; acetonitrile at 0℃; for 0.25h;	72%

2-(chloromethyl)-3-methylnaphthalene-1,4-dione (31599-79-8) + C33H52 + trimethylaluminum (75-24-1) → menaquinone-7 (2124-57-4)

Conditions	Yield
Stage #1: C33H52; trimethylaluminum With zirconocene dichloride In toluene at 0℃; for 1h; Stage #2: 2-(chloromethyl)-3-methylnaphthalene-1,4-dione With bis(triphenylphosphine)nickel(II) chloride; n-butyllithium In tetrahydrofuran; hexane at -20℃; for 1h;	65%

(2E,6E)-farnesyl acetate (4128-17-0) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: salicylic acid; selenium(IV) oxide; tert.-butylhydroperoxide / water; dichloromethane / 24 h / 0 - 20 °C 2.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 3.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 4.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 5.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 5.2: -78 - 20 °C 6.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 7.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 8.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 9.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 9.2: 4.5 h / 0 °C / Inert atmosphere 10.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 11 steps 1.1: salicylic acid; selenium(IV) oxide; tert.-butylhydroperoxide / water; dichloromethane / 24 h / 0 - 20 °C 2.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 3.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 4.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 5.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 5.2: -78 - 20 °C 6.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 7.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 8.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 9.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 10.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 10.2: 5 h / 0 °C / Inert atmosphere 11.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 11 steps 1.1: selenium(IV) oxide; salicylic acid; tert.-butylhydroperoxide / dichloromethane / 14 h / 0 °C 1.2: 2 h 2.1: methanesulfonyl chloride; triethylamine / tetrahydrofuran / 0.75 h / -45 - -40 °C 2.2: 2 h / 0 °C 3.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 3.2: Inert atmosphere 4.1: sodium methylate / methanol / 4 h / 0 °C 5.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 6.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 7.1: triphenylphosphine; bromine / dichloromethane / 0 °C 8.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 8.2: 12 h / Inert atmosphere 9.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 10.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 11.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme

E,E,E-12-hydroxyfarnesyl acetate (93787-91-8) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 2.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 3.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 3.2: -78 - 20 °C 4.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 5.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 7.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 7.2: 4.5 h / 0 °C / Inert atmosphere 8.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 9 steps 1.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 2.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 3.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 3.2: -78 - 20 °C 4.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 5.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 6.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 7.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 8.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 8.2: 5 h / 0 °C / Inert atmosphere 9.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 10 steps 1.1: methanesulfonyl chloride; triethylamine / tetrahydrofuran / 0.75 h / -45 - -40 °C 1.2: 2 h / 0 °C 2.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: sodium methylate / methanol / 4 h / 0 °C 4.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 5.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 6.1: triphenylphosphine; bromine / dichloromethane / 0 °C 7.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 7.2: 12 h / Inert atmosphere 8.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 9.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 10.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme

(2E,6E,10E)-3,7,11-trimethyl-12-(phenylsulfonyl)-dodeca-2,6,10-trien-1-yl acetate (1597486-72-0) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 3.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 4.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 5.2: 4.5 h / 0 °C / Inert atmosphere 6.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 3.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 4.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 6.2: 5 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.5 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide / methanol; water / 1 h / 20 °C / pH 12 3.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 5.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 6.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.5 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide / methanol / 1 h / 20 °C / pH 12 3.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 4.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 5.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 6.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

farnesyl bromide (24163-93-7, 24163-94-8, 56881-57-3, 6874-67-5, 28290-41-7) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 3.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 4.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 5.2: 4.5 h / 0 °C / Inert atmosphere 6.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 3.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 4.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 6.2: 5 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 2.1: n-butyllithium / tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide / 1.5 h / -78 °C 2.2: -78 - 0 °C 3.1: sodium methylate / methanol / 2 h / 20 °C / pH 12 4.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 6.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 7.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 8.1: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.5 h / -78 °C 1.2: -78 - 20 °C 2.1: sodium hydroxide / methanol / 1 h / 20 °C / pH 12 3.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 4.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 5.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 6.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1.1: pyridine / N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 2.1: n-butyllithium / tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide / 1.5 h / -78 °C 2.2: 5 h / -78 °C 3.1: sodium methylate; methanol / 2 h / 20 °C 4.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 5.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 6.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 7.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 8.1: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

C38H56O4S (1597487-01-8) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 2.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 3.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 4.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 4.2: 4.5 h / 0 °C / Inert atmosphere 5.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 2.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 3.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 4.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 5.2: 5 h / 0 °C / Inert atmosphere 6.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol; water / 1 h / 20 °C / pH 12 2: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 4: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 5: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 6: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: sodium hydroxide / methanol / 1 h / 20 °C / pH 12 2: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 3: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 4: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 5: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 6: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

(2E,6E,10E,14E,18E)-3,7,11,15,19,23-hexamethyl-12-(phenylsulfonyl)tetracosa-2,6,10,14,18,22-hexaen-1-ol (1597486-78-6) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 3.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 3.2: 4.5 h / 0 °C / Inert atmosphere 4.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 2.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 3.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 4.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 4.2: 5 h / 0 °C / Inert atmosphere 5.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 2: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 4: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 5: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 2 h / 0 - 20 °C / Inert atmosphere 2: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 4: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 5: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

(2E,6E,10E)-12-bromo-3,7,11-trimethyl-2,6,10-dodecatrienyl acetate (104423-44-1) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 2.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 4.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 6.2: 4.5 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 8 steps 1.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 2.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 4.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 5.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 7.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 7.2: 5 h / 0 °C / Inert atmosphere 8.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 9 steps 1.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: sodium methylate / methanol / 4 h / 0 °C 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: triphenylphosphine; bromine / dichloromethane / 0 °C 6.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 6.2: 12 h / Inert atmosphere 7.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 8.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 9.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme

(2E,6E,10E,14E,18E)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-1-ol (68778-93-8) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 3.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 3.2: 5 h / 0 °C / Inert atmosphere 4.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1.1: triphenylphosphine; bromine / dichloromethane / 0 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 12 h / Inert atmosphere 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: triphenylphosphine; bromine / dichloromethane / 0 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 12 h / Inert atmosphere 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 2: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 3: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 2: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 3: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 4: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

1-bromo-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene (74610-00-7) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 2.2: 5 h / 0 °C / Inert atmosphere 3.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 12 h / Inert atmosphere 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 12 h / Inert atmosphere 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 2: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 3: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 2: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 3: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

phenylsulfonyl hexaprenyl bromide (1597486-86-6) → menaquinone-7 (2124-57-4)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 2.2: 4.5 h / 0 °C / Inert atmosphere 3.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme

C62H82O6S2 (1597486-87-7) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 1.2: 4.5 h / 0 °C / Inert atmosphere 2.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme

C56H78O4S (1597486-91-3) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 1.2: 5 h / 0 °C / Inert atmosphere 2.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme

(2E,6E,10E)-3,7,11-trimethyl-12-oxododeca-2,6,10-trien-1-yl acetate (40266-21-5) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 2.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 4.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 4.2: -78 - 20 °C 5.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 6.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 7.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 8.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 9.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 9.2: 5 h / 0 °C / Inert atmosphere 10.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 9 steps 1.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 2.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 4.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 4.2: -78 - 20 °C 5.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 6.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 7.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 8.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 8.2: 4.5 h / 0 °C / Inert atmosphere 9.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 10 steps 1.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.5 h / -10 °C 2.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 3.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 4.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.5 h / -78 °C 4.2: -78 - 20 °C 5.1: sodium hydroxide / methanol; water / 1 h / 20 °C / pH 12 6.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 7.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 8.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 9.1: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 10.1: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme

1,4-diethoxy-2-methyl-3-[(2E)-3-methyl-4-(phenylsulfonyl)-2-buten-1-yl]naphtalene (1597486-65-1) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 2.2: 4.5 h / 0 °C / Inert atmosphere 3.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 2.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 2.2: 5 h / 0 °C / Inert atmosphere 3.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme

Farnesol (106-28-5) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 11 steps 1.1: pyridine / 12 h / 0 - 20 °C / Inert atmosphere 2.1: salicylic acid; selenium(IV) oxide; tert.-butylhydroperoxide / water; dichloromethane / 24 h / 0 - 20 °C 3.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 4.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 5.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 6.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 6.2: -78 - 20 °C 7.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 8.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 9.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 10.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 10.2: 4.5 h / 0 °C / Inert atmosphere 11.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 12 steps 1.1: pyridine / 12 h / 0 - 20 °C / Inert atmosphere 2.1: salicylic acid; selenium(IV) oxide; tert.-butylhydroperoxide / water; dichloromethane / 24 h / 0 - 20 °C 3.1: sodium tetrahydroborate / methanol; tetrahydrofuran / 0.75 h / -10 °C 4.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere 5.1: N,N-dimethyl-formamide / 18 h / 20 °C / Darkness 6.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 6.2: -78 - 20 °C 7.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 8.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride; lithium triethylborohydride / tetrahydrofuran / 1.17 h / 0 °C / Inert atmosphere 9.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 10.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.83 h / -20 °C / Inert atmosphere; Cooling with acetone-dry ice 11.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / Inert atmosphere; Cooling with acetone-dry ice 11.2: 5 h / 0 °C / Inert atmosphere 12.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme
Multi-step reaction with 7 steps 1.1: phosphorus tribromide / tetrahydrofuran / 3 h / 0 °C 2.1: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 2.67 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium hydroxide; water / methanol / 1 h / 20 °C / pH 12 4.1: phosphorus tribromide / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere; Cooling with acetone-dry ice 5.1: sodium hexamethyldisilazane / tetrahydrofuran; N,N-dimethyl-formamide / 0.5 h / -20 - 0 °C / Inert atmosphere; Cooling with acetone-dry ice 6.1: (1,2-bis(diphenylphosphino)ethane)palladium(II) chloride / tetrahydrofuran / 0.08 h / 0 °C / Cooling with acetone-dry ice; Inert atmosphere 6.2: 4.5 h / 0 °C / Inert atmosphere 7.1: ammonium cerium (IV) nitrate / water; dichloromethane; acetonitrile / 0.25 h / 0 °C View Scheme

1,4-dimethoxy-2-methylnaphthalene (53772-19-3) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: titanium tetrachloride / dichloromethane / 2.17 h / -45 - 0 °C / Inert atmosphere 2.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 2.2: 2.25 h / 0 °C 2.3: 0.67 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 3.2: 14 h / Inert atmosphere 4.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 5.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 6.1: iodine / chloroform / 6 h / 20 °C 7.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 7.2: 12 h / Inert atmosphere 8.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 9.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 10.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 10 steps 1.1: titanium tetrachloride / dichloromethane / 2.17 h / -45 - 0 °C / Inert atmosphere 2.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 2.2: 2.25 h / 0 °C 2.3: 0.67 h / Reflux 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 3.2: 14 h / Inert atmosphere 4.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 5.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 6.1: iodine / chloroform / 6 h / 20 °C 7.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 7.2: 12 h / Inert atmosphere 8.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 9.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 10.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: tin(IV) chloride / 1,2-dichloro-ethane / 20 - 80 °C 2: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 3: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 4: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: tin(IV) chloride / 1,2-dichloro-ethane / 5 h / 80 °C 2: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 3: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 4: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

1,4-dimethoxynaphthalene-3-methyl-2-carboxaldehyde (17827-40-6) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: 2.25 h / 0 °C 1.3: 0.67 h / Reflux 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 14 h / Inert atmosphere 3.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 4.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 5.1: iodine / chloroform / 6 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 6.2: 12 h / Inert atmosphere 7.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 8.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 9.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: 2.25 h / 0 °C 1.3: 0.67 h / Reflux 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 14 h / Inert atmosphere 3.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 4.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 5.1: iodine / chloroform / 6 h / 20 °C 6.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 6.2: 12 h / Inert atmosphere 7.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 8.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 9.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

(1,4-dimethoxy-3-methylnaphthalen-2-yl)acetaldehyde (51794-08-2) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 1.2: 14 h / Inert atmosphere 2.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 3.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 4.1: iodine / chloroform / 6 h / 20 °C 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 5.2: 12 h / Inert atmosphere 6.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 7.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 8.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 1.2: 14 h / Inert atmosphere 2.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 3.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 4.1: iodine / chloroform / 6 h / 20 °C 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 5.2: 12 h / Inert atmosphere 6.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 7.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 8.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

4-(1,4-dimethoxy-3-methylnaphthalen-2-yl)-2-methylbut-2-enoic acid ethyl ester → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 2.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 3.1: iodine / chloroform / 6 h / 20 °C 4.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 4.2: 12 h / Inert atmosphere 5.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 6.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 7.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 2.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 3.1: iodine / chloroform / 6 h / 20 °C 4.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 4.2: 12 h / Inert atmosphere 5.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 6.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 7.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

2-[3-(1,4-dimethoxy-3-methylnaphthalen-2-yl)-1-methylpropenyl][1,3]dithiane → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 12 h / Inert atmosphere 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: 12 h / Inert atmosphere 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

(E)-4-(1,4-dimethoxy-3-methylnaphthalen-2-yl)-2-methylbut-2-en-1-ol (94828-29-2) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2.1: iodine / chloroform / 6 h / 20 °C 3.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 3.2: 12 h / Inert atmosphere 4.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 5.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 6.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2.1: iodine / chloroform / 6 h / 20 °C 3.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 3.2: 12 h / Inert atmosphere 4.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 5.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 6.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

4-(1,4-dimethoxy-3-methylnaphthalen-2-yl)-2-methylbut-2-enal (99306-85-1) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: iodine / chloroform / 6 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 12 h / Inert atmosphere 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: iodine / chloroform / 6 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 2.2: 12 h / Inert atmosphere 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

2-(2,6,10-trimethylundeca-1,5,9-trienyl)[1,3]dithiane → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: sodium methylate / methanol / 4 h / 0 °C 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: triphenylphosphine; bromine / dichloromethane / 0 °C 6.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 6.2: 12 h / Inert atmosphere 7.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 8.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 9.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 9 steps 1.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 2.1: sodium methylate / methanol / 4 h / 0 °C 3.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 4.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 5.1: triphenylphosphine; bromine / dichloromethane / 0 °C 6.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 6.2: 12 h / Inert atmosphere 7.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 8.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 9.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

menadione (58-27-5) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 12 steps 1.1: water; sodium dithionite / ethyl acetate; water / Inert atmosphere 2.1: potassium carbonate / acetone / 6 h / Reflux 3.1: titanium tetrachloride / dichloromethane / 2.17 h / -45 - 0 °C / Inert atmosphere 4.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 4.2: 2.25 h / 0 °C 4.3: 0.67 h / Reflux 5.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 5.2: 14 h / Inert atmosphere 6.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 7.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 8.1: iodine / chloroform / 6 h / 20 °C 9.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 9.2: 12 h / Inert atmosphere 10.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 11.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 12.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 12 steps 1.1: water; sodium dithionite / ethyl acetate / Inert atmosphere 2.1: potassium carbonate / acetone / 6 h / Reflux 3.1: titanium tetrachloride / dichloromethane / 2.17 h / -45 - 0 °C / Inert atmosphere 4.1: potassium tert-butylate / tetrahydrofuran / 0.5 h / 0 °C 4.2: 2.25 h / 0 °C 4.3: 0.67 h / Reflux 5.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 5.2: 14 h / Inert atmosphere 6.1: diisobutylaluminium hydride / tetrahydrofuran / 6 h / Inert atmosphere 7.1: dipyridinium dichromate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 8.1: iodine / chloroform / 6 h / 20 °C 9.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 9.2: 12 h / Inert atmosphere 10.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 11.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 12.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1: sodium dithionite / ethyl acetate; water / 0.33 h / 20 °C / Inert atmosphere 2: potassium carbonate / acetone / 6 h / Reflux 3: tin(IV) chloride / 1,2-dichloro-ethane / 20 - 80 °C 4: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / -20 °C 5: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 6: ammonium cerium (IV) nitrate / water; acetonitrile / 0.75 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: sodium dithionite / ethyl acetate; water / 0.33 h / 20 °C / Inert atmosphere 2: potassium carbonate / acetone / 6 h / Reflux 3: tin(IV) chloride / 1,2-dichloro-ethane / 5 h / 80 °C 4: potassium tert-butylate / tetrahydrofuran; N,N-dimethyl-formamide / 1 h / -20 °C 5: (1,2-bis(diphenylphosphanyl)ethane)dichloridopalladium(II); lithium triethylborohydride / tetrahydrofuran / 4 h / 0 °C / Inert atmosphere 6: ammonium cerium (IV) nitrate / water; acetonitrile; dichloromethane / 0.75 h / 0 °C View Scheme

Farnesal (502-67-0) → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: iodine / chloroform / 6 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 2.2: Inert atmosphere 3.1: sodium methylate / methanol / 4 h / 0 °C 4.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 5.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 6.1: triphenylphosphine; bromine / dichloromethane / 0 °C 7.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 7.2: 12 h / Inert atmosphere 8.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 9.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 10.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 10 steps 1.1: iodine / chloroform / 6 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C / Inert atmosphere 3.1: sodium methylate / methanol / 4 h / 0 °C 4.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 5.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 6.1: triphenylphosphine; bromine / dichloromethane / 0 °C 7.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 7.2: 12 h / Inert atmosphere 8.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 9.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 10.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

acetic acid 3,7,11-trimethyl-12-[2-(2,6,10-trimethylundeca-1,5,9-trienyl)[1,3]dithian-2-yl]-dodeca-2,6,10-trienyl ester → menaquinone-7 (2124-57-4)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: sodium methylate / methanol / 4 h / 0 °C 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: triphenylphosphine; bromine / dichloromethane / 0 °C 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 5.2: 12 h / Inert atmosphere 6.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 7.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 8.1: ammonium cerium (IV) nitrate / water; acetonitrile / 4.08 h / 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: sodium methylate / methanol / 4 h / 0 °C 2.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 3.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 4.1: triphenylphosphine; bromine / dichloromethane / 0 °C 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 5.2: 12 h / Inert atmosphere 6.1: Dess-Martin periodane; water / dichloromethane; acetonitrile / 20 °C 7.1: hydrazine; potassium hydroxide / diethylene glycol / 4 h / 60 - 215 °C / Inert atmosphere; Reflux 8.1: ammonium cerium (IV) nitrate / acetonitrile / 4.08 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) + propionic acid anhydride (123-62-6) → 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalene-1,4-diyl dipropionate (1453189-07-5)

Conditions	Yield
With sodium acetate; zinc at 130℃; for 0.5h;	66%
With sodium acetate; zinc at 130℃; for 0.5h;	66%

menaquinone-7 (2124-57-4) + benzoic acid anhydride (93-97-0) → 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyl-octacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalene-1,4-diyl dibenzoate (1453189-00-8)

Conditions	Yield
With sodium acetate; zinc at 140℃; for 1h;	50%
Stage #1: menaquinone-7; benzoic acid anhydride With sodium acetate; zinc at 140℃; for 1h; Stage #2: With diethylamine In tetrahydrofuran at 20℃; for 1h;	50%

menaquinone-7 (2124-57-4) + 4-(trifluoromethyl)benzoic anhydride (25753-16-6) → 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalene-1,4-diyl bis(4-(trifluoromethyl)benzoate) (1453189-14-4)

Conditions	Yield
With sodium acetate; zinc at 170℃; for 23h;	11%
Stage #1: menaquinone-7; 4-(trifluoromethyl)benzoic anhydride With sodium acetate; zinc at 170℃; for 23h; Stage #2: With diethylamine In tetrahydrofuran at 20℃; for 1h;	11%

menaquinone-7 (2124-57-4) + acetic anhydride (108-24-7) → 1,4-diacetoxy-2-methyl-3-(3,7,11,15,19,23,27-heptamethyl-octacosaheptaen-(2t,6t,10t,14t,18t,22t,26)-yl)-naphthalene (122726-03-8)

Conditions	Yield
With sodium acetate; zinc
With sodium acetate; zinc

menaquinone-7 (2124-57-4) → 3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-4-hydroxy-2-methylnaphthalen-1-yl benzoate (1453189-02-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C View Scheme

menaquinone-7 (2124-57-4) → 4-((diethoxyphosphoryl)oxy)-2-((2E,6E, 10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate (1453189-03-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3.1: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme

menaquinone-7 (2124-57-4) → 4-((diethoxyphosphoryl)oxy)-3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-2-methylnaphthalen-1-yl benzoate (1453189-04-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3.1: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme

menaquinone-7 (2124-57-4) → 4-(((tert-butoxycarbonyl)glycyl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate (1453189-05-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 4-(((tert-butoxycarbonyl)-L-valyl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate (1453189-06-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-4-hydroxy-3-methylnaphthalen-1-yl propionate (1453189-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C View Scheme

menaquinone-7 (2124-57-4) → 4-((diethoxyphosphoryl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl propionate (1453189-10-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3: triethylamine / dichloromethane / 20 h / 0 - 20 °C View Scheme

menaquinone-7 (2124-57-4) → 3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-2-methyl-4-(propionyloxy)naphthalen-1-yl (tert-butoxycarbonyl)-L-valinate

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 4-(((tert-butoxycarbonyl)glycyl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl propionate (1453189-12-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-2-methyl-4-(propionyloxy)naphthalen-1-yl 3-((tert-butoxycarbonyl)amino)propanoate (1453189-13-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3: dmap; dicyclohexyl-carbodiimide / dichloromethane / 20 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 4-((3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-2-methyl-4-(propionyloxy)naphthalen-1-yl)oxy)-4-oxobutanoic acid (1453189-15-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C 3: dmap / dichloromethane / 3.5 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: sodium acetate; zinc / 0.5 h / 130 °C 2: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C 3: dmap / dichloromethane / 3.5 h / 20 °C View Scheme

menaquinone-7 (2124-57-4) → 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-4-hydroxy-3-methylnaphthalen-1-yl benzoate (1453189-01-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium acetate; zinc / 1 h / 140 °C 2: lithium hydroxide; water / tetrahydrofuran / 20 h / 50 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium acetate; zinc / 1 h / 140 °C 1.2: 1 h / 20 °C 2.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 20 h / 50 °C View Scheme

menaquinone-7 (2124-57-4) + acetic anhydride (108-24-7) → acetic acid 3-(3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaenyl)-4-hydroxy-2-methyl-naphthalen-1-yl ester

Conditions	Yield
With sodium acetate; zinc for 0.5h; Inert atmosphere; Reflux;

Upstream product

• 74610-01-8 heptaprenyl bromide 
• 77551-14-5 betulaprenol 6 
• 31599-79-8 2-(chloromethyl)-3-methylnaphthalene-1,4-dione 
• 75-24-1 trimethylaluminum 
• 105-87-3 3,7-dimethyl-2E,6-octadien-1-yl acetate 
• 37905-03-6 8-hydroxygeranyl acetate 
• 37905-04-7 (2E,6E)-8-bromo-3,7-dimethylocta-2,6-dienyl acetate 
• 73875-18-0 (2′E)-2-(3′-methyl-4′-phenylsulfonylbut-2′-enyl)-1,4-dimethoxy-3-methylnaphthalene 
• 59277-17-7 1-(benzenesulfonyl)-2-methyl-4-chloro-2-butene 
• 1575605-23-0 C₃₈H₅₆O₄S 

Downstream Products

• 39776-47-1 menaquinol 
• 1453189-00-8 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyl-octacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalene-1,4-diyl dibenzoate 
• 1453189-14-4 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalene-1,4-diyl bis(4-(trifluoromethyl)benzoate) 
• 1453189-01-9 2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-4-hydroxy-3-methylnaphthalen-1-yl benzoate 
• 1453189-06-4 4-(((tert-butoxycarbonyl)-L-valyl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate 
• 1453189-05-3 4-(((tert-butoxycarbonyl)glycyl)oxy)-2-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate 
• 1453189-04-2 4-((diethoxyphosphoryl)oxy)-3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-2-methylnaphthalen-1-yl benzoate 
• 1453189-03-1 4-((diethoxyphosphoryl)oxy)-2-((2E,6E, 10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-3-methylnaphthalen-1-yl benzoate 
• 1453189-02-0 3-((2E,6E,10E,14E,18E,22E)-3,7,11,15,19,23,27-heptamethyloctacosa-2,6,10,14,18,22,26-heptaen-1-yl)-4-hydroxy-2-methylnaphthalen-1-yl benzoate 

Relevant articles and documents

PROCESS OF VITAMIN K2 DERIVATIVES PREPARATION

The invention relates to an improved process of vitamin K2 derivatives preparation via the alkylation of the menadione-cyclopentadiene adduct.

PROCESS OF VITAMIN K2 DERIVATIVES PREPARATION

Provided is an improved process of vitamin K2 derivatives preparation, represented by formula (I) wherein n is an integer from 3 to 13.

Convergent synthesis of menaquinone-7 (MK-7)

A practical synthesis of menaquinone-7 (MK-7, vitamin K2) in the all-Trans form was designed. Stereoselective synthesis of MK-7 was achieved through a "1 + 6" convergent strategy by condensation of two building blocks, menadione monoprenyl derivative (fragment "1") with hexaprenyl bromide (fragment "6", 82%). Pd-catalyzed desulfonation with LiEt3BH (78%) was followed by oxidation of the hydroquinone moiety using ammonium cerium(IV) nitrate (72%). The major challenge in our methodology was the preparation of all-Trans hexaprenyl bromide by coupling of two triprenyl units derived from trans,trans-farnesol. Manufacturing on a pilot scale was accomplished through our approach. The scalable method was designed especially for a large, kilogram-scale production from easily available intermediates. Furthermore, the proposed methodology avoids many chromatographic purifications and allows for a relatively cost-effective manufacturing. Moreover, our synthesis yielded high-purity (99.9%) final product MK-7, which can be used as a dietary supplement as well as an active pharmaceutical ingredient.