39746-01-5

Basic information

• Product Name: (-)-Corey aldehyde benzoate
• Synonyms: BENZOIC ACID (3AR,4R,5R,6AS)-4-FORMYL-2-OXO-HEXAHYDRO-CYCLOPENTA[B]FURAN-5-YL ESTER;[3ar(3aα,4α,5β,6aα)]-(-)-5-(benzoyloxy)hexahydro-2-oxo-2h-cyclopenta[b]furan-4-carboxaldehyde;(-)-Corey aldehyde benzoate;3β-Benzoyloxy-2β-carboxaldehyde-5α-hydroxy-1α-cyclopentaneacetic Acid γ-Lactone;(3AR,4R,5R,6AS)-5-(BENZOYLOXY)HEXAHYDRO-2-OXO-2H-CYCLOPENTA[B]FURAN-4-CARBOXALDEHYDE;[3AR(3A-ALPHA,4ALPHA,5BETA,6A-ALPHA)]-(-)-5-(BENZOYLOXY)HEXAHYDRO-2-OXO-2 H-CYCLOPENTA[B]FURAN-4-CARBOXALDEHYDE;[3ar(3aa,4a,5b,6aa)]-(-)-5-(benzoyloxy)hexahydro-2-oxo-2h-cyclopenta[b]furan-4-carboxaldehyde;COREY ALDEHYDE BENZOATE
• CAS NO: 39746-01-5
• Molecular Formula: C₁₅H₁₄O₅
• Molecular Weight: 274.27
• Mol File: 39746-01-5.mol

Chemical Properties

• Melting Point: 128-138 °C(lit.)
• Boiling Point: 470.427 °C at 760 mmHg
• Flash Point: 211.802 °C
• Appearance: /
• Density: 1.33 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.577
• Storage Temp.: ?20°C
• CAS DataBase Reference: (-)-Corey aldehyde benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-Corey aldehyde benzoate(39746-01-5)
• EPA Substance Registry System: (-)-Corey aldehyde benzoate(39746-01-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 39746-01-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(-)-Corey aldehyde benzoate is used as a key intermediate for the synthesis of prostaglandin analogues, which are essential in the development of various pharmaceutical products. These analogues have a wide range of applications, including the treatment of various medical conditions such as inflammation, pain, and cardiovascular diseases.
In the synthesis of human FP-receptor selective prostaglandin analogues, (-)-Corey aldehyde benzoate serves as a vital component due to its chiral nature. This allows for the creation of specific prostaglandin analogues that can selectively target the human FP-receptor, leading to more effective and targeted treatments for related medical conditions.
Overall, (-)-Corey aldehyde benzoate is a valuable compound in the pharmaceutical industry, contributing to the development of innovative and effective treatments for a variety of health issues. Its unique properties and versatility make it an essential component in the synthesis of prostaglandin analogues, which have significant potential in the treatment of various medical conditions.

InChI:InChI=1/C15H14O5/c16-8-11-10-6-14(17)19-12(10)7-13(11)20-15(18)9-4-2-1-3-5-9/h1-5,8,10-13H,6-7H2/t10-,11-,12+,13-/m1/s1

Synthetic route

(1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4) → (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5)

Conditions	Yield
With Dess-Martin periodane In dichloromethane at 0 - 20℃; for 1h;	100%
With Dess-Martin periodane In dichloromethane at 0 - 10℃; for 2h;	96.7%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; carbonic acid dimethyl ester In ethyl acetate at 0 - 5℃; Inert atmosphere;	95.6%

(1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4) → (1S,5S)-3-oxo-2-oxabicyclo<3.3.0>oct-6-en-6-carbaldehyde (51260-12-9) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5)

Conditions	Yield
With sulfur trioxide pyridine complex Inert atmosphere;

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5S)-3-oxo-2-oxabicyclo<3.3.0>oct-6-en-6-carbaldehyde (51260-12-9)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -78℃; for 1h; Elimination;	100%

dimethyl (7-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonate (500871-68-1) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-(E)-8-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

Conditions	Yield
Stage #1: dimethyl (7-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 0 - 20℃; for 2.5h; Inert atmosphere;	100%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → Benzoic acid (3aR,4R,5R,6aS)-4-((E)-2-ethoxycarbonyl-vinyl)-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester (1027275-03-1)

Conditions	Yield
In benzene at 20℃; for 0.5h; Wittig reaction;	98%

1-(triphenylphosphoranylidene)-2-hexanone (41693-11-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C21H24O5

Conditions	Yield
In dichloromethane at 20 - 25℃; for 8h; Wittig Olefination;	97.1%

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,6aS)-4-((E)-3-Oxo-oct-1-enyl)-3,3a,6,6a-tetrahydro-cyclopenta[b]furan-2-one (49673-16-7) + (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Horner-Emmons reaction;	A 1% B 96%

2-oxohexylphosphonic acid dimethyl ester (61728-15-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	96%

(2,2-difluoro-3-phenoxypropyl) diethyl phosphate + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybutan-1-en-1-yl)-hexahydro-2-oxo-2H-cyclopenta[b]furan-5-yl benzoate (209861-00-7)

Conditions	Yield
Stage #1: (2,2-difluoro-3-phenoxypropyl) diethyl phosphate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 30℃; for 0.25h; Inert atmosphere; Cooling with ice; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 40℃; for 2h;	93.6%

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
Stage #1: dimethyl 2-oxoheptylphosphonate With lithium hydroxide In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether; water at 20℃; for 1h;	91.5%
Stage #1: dimethyl 2-oxoheptylphosphonate; (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one With lithium chloride In tetrahydrofuran; dichloromethane at -20℃; for 2.5h; Stage #2: With triethylamine In tetrahydrofuran; dichloromethane at -5℃; for 19h;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (51638-91-6)

Conditions	Yield
With sodium hydride Horner-Emmons reaction;	90%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydride; zinc(II) chloride In tetrahydrofuran; mineral oil at 25 - 35℃; for 0.416667h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; dichloromethane; mineral oil at 25 - 40℃; for 2.08333h; Inert atmosphere;	61%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydroxide; zinc(II) chloride In tetrahydrofuran at 27℃; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at 27℃; for 15h; Inert atmosphere;	50%

4-phenyl-1-(1-phenyl-1H-tetrazole-5-sulfonyl)butan-2-one (1174193-89-5) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3)

Conditions	Yield
With potassium tert-butylate In dichloromethane; tert-butyl alcohol at -60 - -55℃; Solvent; Inert atmosphere;	89.43%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In acetonitrile at -15℃; Wittig Reaction;	84.7%
With triethylamine; lithium chloride In tetrahydrofuran; dichloromethane at 0℃; for 2h; Horner-Wadsworth-Emmons Olefination; Cooling with ice;	73%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Metallation; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane Condensation;
With n-butyllithium In tetrahydrofuran; hexane; dichloromethane; acetic acid
With triethylamine; lithium chloride In dichloromethane at 0℃; for 2h; Horner-Emmons reaction;

dimethyl diazo-2-oxopropylphosphonate (815610-17-4) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C16H14O4

Conditions	Yield
With potassium carbonate In methanol at 0 - 5℃; for 12.5h;	81.9%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + dimethyl (2-oxoheptyl)phosphonate → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
Stage #1: dimethyl (2-oxoheptyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 20℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at 20℃; for 1.5h;	80%

1-(triphenylphosphoranylidene)-2-heptanone (33803-58-6) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
at 20 - 30℃; for 8h; Time; Wittig Olefination;	79.2%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + {2-[(3-methoxymethyl-phenyl)methyl]-2-oxo-ethyl}phosphonic acid dimethyl ester (256382-39-5) → (3aR,4R,5R,6aS)-4-[(1E)-4-[3-(methoxymethyl)phenyl]-3-oxo-1-buten-1-yl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate (1175629-43-2)

Conditions	Yield
Stage #1: {2-[(3-methoxymethyl-phenyl)methyl]-2-oxo-ethyl}phosphonic acid dimethyl ester With sodium hydride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran for 0.5h; Honer-Emmons reaction; Inert atmosphere;	73.7%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4)

Conditions	Yield
With sodium tetrahydroborate In methanol; dichloromethane at 0℃; for 0.416667h;	69%
With sodium tetrahydroborate In methanol
With sodium tetrahydroborate In methanol; dichloromethane

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + dimethyl [3-(2-iodo-5-trifluoromethyl-phenoxy)-2-oxo-propyl]-phosphonate (336625-17-3) → Benzoic acid (3aR,4R,5R,6aS)-4-[(E)-4-(2-iodo-5-trifluoromethyl-phenoxy)-3-oxo-but-1-enyl]-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester (336625-19-5)

Conditions	Yield
With triethylamine; lithium chloride In tetrahydrofuran at 5 - 20℃; for 3.33333h;	60%

C15H27(2)H6O5PSi (1352751-86-0) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C28H34(2)H6O6Si

Conditions	Yield
With triethylamine In tetrahydrofuran at -10 - 20℃; Inert atmosphere;	54%

Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5R,6R,7R)-7-(benzoyloxy)-6-vinyl-2-oxabicyclo[3.3.0]octan-3-one (618387-07-8)

Conditions	Yield
Stage #1: Methyltriphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran at -30℃; for 0.5h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere;	51%
With potassium tert-butylate In tetrahydrofuran Wittig olefination;

dimethyl 4-(3-trifluoromethylphenyl)-2-oxobutylphosphonate (70783-99-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-[(E)-3-oxo-5-(3-trifluoromethyl-phenyl)-pent-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (294856-03-4)

Conditions	Yield
Stage #1: dimethyl 4-(3-trifluoromethylphenyl)-2-oxobutylphosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Metallation; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane Condensation;	50%

dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate (50889-46-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-((E)-4,4-difluoro-3-oxooct-1-enyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

Conditions	Yield
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With lithium hydroxide In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether; water at 20℃; for 3h; Product distribution / selectivity;	49.5%
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With lithium hydride In tert-butyl methyl ether at 20℃; for 2h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether at 20℃; for 6h; Product distribution / selectivity;	4.8%
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; mineral oil at 26℃; for 0.5h; Inert atmosphere; Stage #3: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 25 - 45℃; for 20h;

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4) + Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-((Z)-3-oxo-oct-1-enyl)-hexahydro-cyclopenta[b]furan-5-yl ester

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Horner-Emmons reaction;	A n/a B 20%

diazomethane (186581-53-3, 908094-01-9) + methyl 2,2,5-trimethylhex-4-enoate (66478-19-1) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.10Z.13E)-(8R.12R.15S)-15-Hydroxy-9-oxo-16.16.19-trimethyl-5.10.13.18-prostatetraensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + methyllithium (917-54-4) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15R)-15-Hydroxy-9-oxo-11.19-dimethyl-5.13.18-prostatriensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + methyllithium (917-54-4) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15S)-15-Hydroxy-9-oxo-11.19-dimethyl-5.13.18-prostatriensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + methylmagnesium bromide (75-16-1) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.10Z.13E)-(8R.12R.15RS)-15-Hydroxy-9-oxo-15.19-dimethyl-5.10.13.18-prostatetraensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15S)-9-Oxo-11.15-dihydroxy-19-methyl-5.13.18-prostatriensaeuremethylester (66477-71-2)

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (8R.9S.11R.12R.15R)-9.11.15-Trihydroxy-19-methyl-18-prostensaeuremethylester (66477-98-3)

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.12R.15S)-15-Hydroxy-9-oxo-19-methyl-5.13.18-prostatriensaeure-methylester (66477-82-5)

Conditions	Yield
Multistep reaction;

Upstream product

• 172821-93-1 C₁₅H₁₆O₅ 
• 39746-00-4 (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one 

Downstream Products

• 110828-48-3 Benzoic acid (3aR,5R,6aS)-4-{(E)-5-[2-(tert-butyl-dimethyl-silanyloxy)-4-(trityl-amino)-phenyl]-3-oxo-pent-1-enyl}-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester 
• 185225-06-3 C₂₂H₂₆O₅ 
• 51638-91-6 (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-5-yl benzoate 
• 49673-16-7 (3aR,6aS)-4-((E)-3-Oxo-oct-1-enyl)-3,3a,6,6a-tetrahydro-cyclopenta[b]furan-2-one 
• 40834-86-4 (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester 
• 185225-06-3 Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-((Z)-3-oxo-oct-1-enyl)-hexahydro-cyclopenta[b]furan-5-yl ester 
• 39746-00-4 (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one 
• 66477-56-3 (1S,5R,6R,7R)-7-Benzoyloxy-6-[(E)-7-methyl-3-oxo-1,6-octadienyl]-2-oxabicyclo[3,3,0]octan-3-one 

Relevant articles and documents

Preparation method of carboprost tromethamine intermediate

The invention provides a preparation method of a carboprost tromethamine intermediate. The method comprises the following steps: A) carrying out an oxidation reaction on benzoyl corey lactone alcohol shown in a formula I under the action of a catalyst and an oxidizing agent to obtain benzoyl corey lactone aldehyde shown in a formula II; B) reacting the benzoyl corey lactone aldehyde as shown in the formula II with dimethyl (2-oxoheptyl) phosphonate under the action of alkali to obtain a 15-ketone crude product as shown in a formula III, and recrystallizing the 15-ketone crude product to obtain a 15-ketone pure product; and C) carrying out methylation reaction on the 15-ketone pure product to obtain the carboprost tromethamine intermediate as shown in a formula IV. According to the invention, the use of reagents with high toxicity and serious environmental pollution is avoided; when the carboprost intermediate 15-ketone is prepared, a mixed solvent is adopted for recrystallization, so that column chromatography is omitted, operation is easy and convenient, reagents are saved, and cost is reduced; and in the methylate preparation process, ultralow temperature is avoided, and the reaction time is shortened, so that the energy consumption is reduced, and the purity and the yield are relatively high.

Carprost tromethamine related impurity levobutyl 15-ketone and preparation method thereof

The invention relates to the technical field of compounds and preparation thereof, in particular to a prostaglandin tromethamine related impurity levobutyl 15-ketone and a preparation method thereof.The method comprises the following steps that 1, in the presence of a fifth organic solvent, strong base is used for carrying out dehydrogenation reaction on methyl triphenyl phosphine halide, ethyl butyrate is added after the reaction is carried out for a certain period of time, and a reaction solution is obtained; continuously reacting for a certain time to obtain 1-triphenylphosphine- 2-pentanone; and (2) carrying out wittig reaction on the 1-triphenylphosphine- 2-pentanone obtained in the step (1) and a second organic solvent solution of benzoyl corey lactone aldehyde to obtain butyl-15 ketone. The method has the characteristics that the operation is simple and convenient, the safety is high, the yield and the purity of the obtained product are high under optimal conditions, the requirements for impurity research can be met, and the like.

Carboprost tromethamine related impurity L-amyl 15-ketone and preparation method thereof

The invention relates to a carboprost tromethamine related impurity L-amyl 15-ketone and a preparation method thereof. The preparation method comprises the following steps of: (1) in the presence of afifth organic solvent, carrying out dehydrogenation reaction on methyl triphenyl phosphine halide by using strong base, adding ethyl valerate after reaction for a certain time, continuously reactingfor a certain time to obtain 1-triphenylphosphine 2-hexanone; and (2) carrying out wittig reaction on the 1-triphenylphosphine 2-hexanone obtained in the step (1) and a second organic solvent solutionof benzoyl corey lactone aldehyde to obtain a pentyl-15 ketone crude product. The method has the advantages of simple and convenient operation, high safety, and high yield and purity of an obtained product under optimal conditions, and can meet the requirements for impurity research.

Synthetic method of alfaprostol

The invention relates to the field of medicine preparation, and particularly relates to a synthetic method of alfaprostol. The synthesis method comprises the following steps: subjecting levobenzoyl corey lactone adopted as a raw material to oxidization by primary alcohol, and reaction with azido phosphate to obtain a compound a3; inducing chiral addition of the compound a3 and aldehyde by chiral ligand amine to generate a compound a4; performing reduction and a Wittig reaction to generate a compound a6; and finally, carrying out methylation reaction on terminal carboxyl of the compound a6 to prepare the alfaprostol. According to the synthesis method of the alfaprostol, provided by the invention, the levobenzoyl corey lactone is directly used as a raw material, the raw material is simple and easy to obtain, and the operation is simple; reaction steps are short, the yield of the whole process route is about 55-60%, and industrial production is easy to realize; the process conditions of each step of reaction are easy to realize, post-treatment is simple, and intermediates are easy to purify; only one-step chiral reaction is adopted, isomer impurities are easy to control, and the obtained product is high in optical purity.

15-ketone preparation method

The present invention relates to a drug intermediate 15-ketone preparation method in chemical field. The preparation method comprises the following steps: (1) (-)-Corey lactone benzoate, an oxidizing agent and a catalyst are added into a first organic solvent for oxidation to obtain a reaction solution A; (2) after a dilute acid is dropwise added into the reaction solution A obtained in the step (1), the solution is stirred and filtered, the filtrate is extracted directly with the first organic solvent, an organic phase is washed with water, dehydrated with a desiccant and filtered to obtain a (-)-Corey lactone benzoate aldehyde solution; (3) Wittig reagent is added into the (-)-Corey lactone benzoate aldehyde solution obtained in the step (2) for Wittig reaction to obtain a reaction solution B, the reaction solution B is concentrated, a second organic solvent is added, and after cooling and crystallization, a crystallization liquid is obtained; and (4) the crystallization liquid obtained in the step (3) is filtered, the filter cake is washed with a third organic solvent, the filter cake is dissolved by the first organic solvent for impurity removal, and after filteration and concentration, an oil matter is obtained. The drug intermediate 15-ketone preparation method has the advantages of good product quality and the like.

PREPARATION OF LUBIPROSTONE

Aspects of the present application relate to process for the preparation of lubiprostone.

Improved Process for the Production of Prostaglandins and Prostaglandin Analogs

The present invention relates to an improved process for the production of prostaglandins and prostaglandin analogs. In particular, this invention relates to the production of prostaglandins of the PGF2α-series, including latanoprost, travoprost, and bimatoprost, which are active pharmaceutical ingredients used for the reduction of elevated intraocular pressure in patients with glaucoma and ocular hypertension.

An improved synthesis of the selective EP4 receptor agonist ONO-4819

(Chemical Equation Presented) An improved synthesis of the highly selective EP4-receptor agonist ONO-4819 has been developed. The previous synthesis suffered from several drawbacks, in which a critical one is the difficulty in the removal of byproducts leading to unsatisfactory quality of the active pharmaceutical ingredient (API). Furthermore, on stereoselective reduction of an enone intermediate by binaphthol-modified lithium aluminum hydride, low concentration of the reaction conditions and tedious purification procedures to remove excess binaphthol were critical issues for the manufacturing process of the API. In the improved process,we have developed improved conditions using γ-thiobutyrolactone as sulfur source instead of potassium thioacetate to introduce the sulfur-containing C4 side chain without formation of byproducts. For stereoselective synthesis of the chiral alcohol, (-)-DIP-chloride reduction is found to be the best method, which can improve not only the enantioselectivity but also the workload for removing the chiral modifier in a purification process. Furthermore, benzoyl and tert-butyldimethylsilyl groups as protecting groups for hydroxyl functions were used for precise process controls of all intermediates. By changing these protecting groups, the purity of ONO-4819 was strictly controlled through crystalline intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity was developed. 2009 American Chemical Society.

Method for preparing prostaglandin derivative

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METHOD FOR PREPARING PROSTAGLANDIN DERIVATIVE

A method for preparing a prostaglandin derivative represented by the following general formula (I): (wherein Ph represents phenyl group, R1 represents a C1-7 alkyl group, a C1-7 alkenyl group, phenyl group, or benzyl group), which comprises the successive steps (1) to (8) described in the specification, or any one step or two or more successive steps selected from the group consisting of the steps (1) to (8). A method for efficiently, inexpensively and safely preparing prostaglandin derivatives, of which typical example is latanoprost, is provided.