154026-95-6

Basic information

• Product Name: tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate
• Synonyms: tert-butyl (4r-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate;(4r-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester;(4R-CIS)-6-[(ACETYLOXY)METHYL]-2,2-DIMETHYL-1,3-DIOXANE-4-ACETIC ACID, T-BUTYL ESTER;(4r-Cis)6[(Acetyloxymethyl)]-2,2-Dimethyl-1,3-Dimethyl-1,3-Dioxane-4-Acetic Acid, 1,1-Dimethylethyl Ester;2-[(4R,6S)-6-(Acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-buthyl ester;(4R-CIS)-6-[ (ACETYLOXY)METHYL ]-2,2-DIMETHYL-1,;tert-Butyl (4R-cis)-;(4R-Cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester(D5)
• CAS NO: 154026-95-6
• Molecular Formula: C₁₅H₂₆O₆
• Molecular Weight: 302.36
• EINECS: 1806241-263-5
• Product Categories: rosuvastatin intermediates;INTERMEDIATES OF ROSUVASTATIN
• Mol File: 154026-95-6.mol

Chemical Properties

• Boiling Point: 353.142 °C at 760 mmHg
• Flash Point: 150.334 °C
• Appearance: /
• Density: 1.037 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.436
• Storage Temp.: 2-8°C
• CAS DataBase Reference: tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate(154026-95-6)
• EPA Substance Registry System: tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate(154026-95-6)

Safety Data

• Hazardous Substances Data: 154026-95-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate is used as an impurity in the production of Rosuvastatin for the pharmaceutical industry. Its presence is significant as it can affect the quality, safety, and efficacy of the final drug product. The application reason for monitoring and controlling the levels of this impurity is to ensure the overall quality and consistency of Rosuvastatin as a medication for treating high cholesterol and related conditions.
Additionally, understanding the properties and behavior of this impurity can contribute to the optimization of the synthesis process, potentially leading to improved yields and reduced impurity levels in the final product. This, in turn, can enhance the therapeutic benefits and minimize potential side effects associated with the use of Rosuvastatin.

InChI:InChI=1/C15H26O6/c1-10(16)18-9-12-7-11(19-15(5,6)20-12)8-13(17)21-14(2,3)4/h11-12H,7-9H2,1-6H3/t11-,12+/m1/s1

Synthetic route

tetrabutylammonium acetate (10534-59-5) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
at 115℃; for 7h;	99.1%
In 1-methyl-pyrrolidin-2-one at 25 - 95℃; for 24h;	7.2 g

sodium acetate (127-09-3) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
With copper(l) chloride In N,N-dimethyl-formamide at 120 - 130℃; for 24h; Reagent/catalyst; Solvent;	97.6%
With tetrabutylammomium bromide In N,N-dimethyl-formamide at 120℃; for 4h; Solvent;	542.97 g

(3R,5S)-6-acetoxy-3,5-dihydroxyhexanoic acid tert-butyl ester + 2,2-dimethoxy-propane (77-76-9) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
With methanesulfonic acid In toluene at 20℃; for 8h;	95.8%
With methanesulfonic acid In toluene at 0 - 5℃; for 4h;	88.1%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) + acetyl chloride (75-36-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Stage #1: 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate With pyridine In dichloromethane at 20℃; for 0.5h; Stage #2: acetyl chloride In dichloromethane at 20℃; for 1h;	86%
With pyridine In dichloromethane at 20℃; for 0.5h;	15.9 g

ammonium acetate (631-61-8) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 95℃; for 24h;	80%

potassium acetate (127-08-2) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Stage #1: potassium acetate; (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester With tetrabutyl phosphonium bromide In toluene at 105℃; for 22h; Stage #2: With pyrographite In n-heptane; toluene at 20℃;	76%
Stage #1: (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester; 1-ethyl-3-methylimidazolium acetate at 90℃; for 5h; Stage #2: potassium acetate at 90℃; for 23.5h; Product distribution / selectivity;
In 1-ethyl-3-methyl-1H-imidazol-3-ium chloride at 110℃; for 2.5h;

(3R,5S) t-butyl 6-acetoxy-3,5-dihydroxyhexanoate + sodium hydrogencarbonate (144-55-8) + 2,2-dimethoxy-propane (77-76-9) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane; ethyl acetate

chloride (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester + tetrabutylammonium acetate (10534-59-5) + 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
In 1-methyl-pyrrolidin-2-one

potassium acetate (127-08-2) + 1-ethyl-3-methylimidazolium acetate (143314-17-4) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
at 100℃; for 4h;

1-ethyl-3-methylimidazolium acetate (143314-17-4) + (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
at 100℃; for 3h; Product distribution / selectivity;

C13H25ClO4Si → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: sodium tetrahydroborate / water / 14 h / 0 °C 3.1: acetone / 0.25 h / 25 °C 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: diethyl methoxy borane / tetrahydrofuran; methanol / 1 h / 25 °C / Inert atmosphere 2.2: 4 h / -78 °C / Inert atmosphere 3.1: acetone / 0.25 h 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 4 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: sodium tetrahydroborate; sodium dodecyl-sulfate / water / 14 h / 0 °C 3.1: acetone / 0.25 h 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 1 h / 0 °C 2: sodium tetrahydroborate / water / 14 h / 0 °C 3: (R)-10-camphorsulfonic acid / dichloromethane / 3 h / 40 °C 4: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme

(5S)-tert-butyl 6-chloro-3,5-dihydroxyhexanoate (406680-96-4) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetone / 0.25 h / 25 °C 1.2: 6 h / 48 - 50 °C 2.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 2 steps 1: (R)-10-camphorsulfonic acid / dichloromethane / 3 h / 40 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme

tert-butyl 2-((6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate + tetrabutylammonium acetate (10534-59-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) + tert-butyl 2-((4S,6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate

Conditions	Yield
In 1-methyl-pyrrolidin-2-one at 25 - 85℃; for 24h; Overall yield = 7.2 %;	A n/a B n/a

tert-butyl 2-((6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water; dichloromethane / 24 h / 20 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme

Tert-butyl (5S)-6-chloro-5-hydroxy-3-oxohexanoate (154026-92-3) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate / water / 14 h / 0 °C 2.1: acetone / 0.25 h / 25 °C 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 3 steps 1.1: diethyl methoxy borane / tetrahydrofuran; methanol / 1 h / 25 °C / Inert atmosphere 1.2: 4 h / -78 °C / Inert atmosphere 2.1: acetone / 0.25 h 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium tetrahydroborate; sodium dodecyl-sulfate / water / 14 h / 0 °C 2.1: acetone / 0.25 h 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme

1,1-dimethylethyl (3R,5S)-6-chloro-3,5-dihydroxy-4-hexanoate (154026-93-4) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: acetone / 0.25 h 1.2: 6 h / 48 - 50 °C 2.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C View Scheme
Multi-step reaction with 2 steps 1: (1S)-10-camphorsulfonic acid / acetone / 6 h / 48 - 50 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 95 °C View Scheme

tert-butyl 2-((6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
With hydrogenchloride In dichloromethane; water at 25℃; for 48h;	n/a

C6H9NO3 → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: zinc; methanesulfonic acid / tetrahydrofuran / 0.5 h / Reflux 2: D-glucose; potassium dihydrogenphosphate; dipotassium hydrogenphosphate / 25 - 28 °C 3: methanesulfonic acid / toluene / 4 h / 0 - 5 °C View Scheme

tert-butyl 6-acetoxy-3,5-dioxohexanoate → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: glucose dehydrogenase; nicotinamide adenine dinucleotide phosphate / N,N-dimethyl-formamide / 25 °C / pH 6.5 / Enzymatic reaction 2: methanesulfonic acid / toluene / 8 h / 20 °C View Scheme

tert-butyl 4-chloroacetoacetate (74530-56-6) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanesulfonic acid / 6 h / 20 - 60 °C 2.1: ethyl bromide; magnesium; iodine / tetrahydrofuran / 50 - 60 °C 2.2: -10 - 40 °C 3.1: glucose dehydrogenase; nicotinamide adenine dinucleotide phosphate / N,N-dimethyl-formamide / 25 °C / pH 6.5 / Enzymatic reaction 4.1: methanesulfonic acid / toluene / 8 h / 20 °C View Scheme

[2-chloromethyl-[1,3]-dioxolane-2-yl]acetic acid tert-butyl ester → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: ethyl bromide; magnesium; iodine / tetrahydrofuran / 50 - 60 °C 1.2: -10 - 40 °C 2.1: glucose dehydrogenase; nicotinamide adenine dinucleotide phosphate / N,N-dimethyl-formamide / 25 °C / pH 6.5 / Enzymatic reaction 3.1: methanesulfonic acid / toluene / 8 h / 20 °C View Scheme

[2-bromomethyl-[1,3]-dioxolane-2-yl]acetic acid tert-butyl ester → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc; chloro-trimethyl-silane; ethyl bromide / tetrahydrofuran / 60 - 65 °C 1.2: 0 - 40 °C 2.1: glucose dehydrogenase; nicotinamide adenine dinucleotide phosphate / N,N-dimethyl-formamide / 25 °C / pH 6.5 / Enzymatic reaction 3.1: methanesulfonic acid / toluene / 8 h / 20 °C View Scheme

tert-butyl 4-bromoacetoacetate (74530-57-7) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: methanesulfonic acid / 6 h / 20 - 60 °C 2.1: zinc; chloro-trimethyl-silane; ethyl bromide / tetrahydrofuran / 60 - 65 °C 2.2: 0 - 40 °C 3.1: glucose dehydrogenase; nicotinamide adenine dinucleotide phosphate / N,N-dimethyl-formamide / 25 °C / pH 6.5 / Enzymatic reaction 4.1: methanesulfonic acid / toluene / 8 h / 20 °C View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxane-4-yl)acetic acid (154877-92-6)

Conditions	Yield
With sodium hydroxide In methanol; water at 60℃; for 20h;	100%

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With potassium carbonate In methanol; water	98%
With methanol; potassium carbonate for 0.5h;	98%
With methanol; potassium carbonate at 20℃;	92%

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate (124752-23-4)

Conditions	Yield
Stage #1: (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester With methanol; potassium carbonate for 3h; Stage #2: With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane at -5 - 5℃; for 1h;	96.1%
Multi-step reaction with 2 steps 1: potassium carbonate; methanol / 0.5 h 2: copper(l) chloride; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen / acetonitrile; dichloromethane / 25 - 40 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / dichloromethane; methanol 2: triethylamine; oxalyl dichloride / dichloromethane; dimethyl sulfoxide View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → (3R,5S)-6-acetoxy-3,5-dihydroxyhexanoic acid tert-butyl ester

Conditions	Yield
With acetic acid In tetrahydrofuran at 20℃; for 2h;	90%

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → (4R,6S)-(E)-{6-[2-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid tert-butyl ester (147489-06-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate; methanol / 0.5 h 2: potassium carbonate / dimethyl sulfoxide / 3 h / 70 °C View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) + 1-thiopropane (107-03-9) → [(4R,6S)-6-hydroxymethyl-2,2-dimethyl[1,3]dioxan-4-yl]thioacetic acid S-propyl ester

Conditions	Yield
Stage #1: (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester With sodium hydroxide In methanol; water at 15 - 70℃; Stage #2: 1-thiopropane With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at -2 - 2℃;

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → C12H20O4S

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol; water / 15 - 70 °C 1.2: -2 - 2 °C 2.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hydrogencarbonate; sodium hypochlorite / dichloromethane / -2 - 35 °C View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → (3R,5S)-6-<(methylsulfonyl)oxy>-3,5-O-isopropylidene-3,5-dihydroxyhexanoic acid tert-butyl ester (135054-68-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / methanol / -2 - 2 °C 2: triethylamine / dichloromethane View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → [(4R,6S)-2,2-dimethyl-6-(1-phenyl-1H-tetrazol-5-ylsulfanylmethyl)[1,3]dioxan-4-yl]acetic acid tert-butyl ester (380460-39-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / methanol / -2 - 2 °C 2: triethylamine / dichloromethane 3: N,N-dimethyl-formamide / 25 - 130 °C View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → [(4R,6S)-2,2-dimethyl-6-(1-phenyl-1H-tetrazole-5-sulfonylmethyl)[1,3]dioxan-4-yl]acetic acid tert-butyl ester (380460-37-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / methanol / -2 - 2 °C 2: triethylamine / dichloromethane 3: N,N-dimethyl-formamide / 25 - 130 °C 4: hexaammonium heptamolybdate tetrahydrate; dihydrogen peroxide / isopropyl alcohol View Scheme

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → 2-[(4R,6S)-6-[(E)-2-[4-(4-fluorophenyl)-2-(N-methylmethanesulfonamido)-6-(isopropyl)pyrimidin-5-yl]vinyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert butyl ester (289042-12-2)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / methanol / -2 - 2 °C 2: triethylamine / dichloromethane 3: N,N-dimethyl-formamide / 25 - 130 °C 4: hexaammonium heptamolybdate tetrahydrate; dihydrogen peroxide / isopropyl alcohol 5: sodium hydride / tetrahydrofuran / 0 - 35 °C View Scheme

Upstream product

• 74530-57-7 tert-butyl 4-bromoacetoacetate 
• 74530-56-6 tert-butyl 4-chloroacetoacetate 
• 77-76-9 2,2-dimethoxy-propane 
• 127-09-3 sodium acetate 
• 154026-94-5 (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester 
• 631-61-8 ammonium acetate 
• 154026-93-4 1,1-dimethylethyl (3R,5S)-6-chloro-3,5-dihydroxy-4-hexanoate 
• 154026-92-3 Tert-butyl (5S)-6-chloro-5-hydroxy-3-oxohexanoate 
• 521973-99-9 tert-butyl 2-((6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 
• 10534-59-5 tetrabutylammonium acetate 
• 406680-96-4 tert-butyl (5S)-6-chloro-3,5-dihydroxyhexanoate 
• 143314-17-4 1-ethyl-3-methylimidazolium acetate 
• 127-08-2 potassium acetate 
• 124655-09-0 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate 

Downstream Products

• 124655-09-0 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate 
• 124752-23-4 tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate 
• 147489-06-3 (4R,6S)-(E)-{6-[2-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid tert-butyl ester 
• 1235588-97-2 tert-butyl 2-((4R,6S)-6-((E)-2-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)vinyl)-2-phenyl-1,3-dioxan-4-yl)acetate 
• 1235588-94-9 tert-butyl 2-((4R,6S)-6-(hydroxymethyl)-2-phenyl-1,3-dioxan-4-yl)acetate 
• 1007871-85-3 tert-butyl-6-[(1E)-2-[4-(4-fluorophenyl)-6-(1-methylethyl)-2-[methyl(methylsulfonyl)amino]-5-pyrimidinyl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-acetate 

Relevant articles and documents

Rosuvastatin calcium intermediate, preparation method thereof and application of intermediate

The invention discloses a rosuvastatin calcium intermediate, a preparation method thereof and an application of the intermediate. The synthesis process of the intermediate is environmentally friendly,simple and convenient to operate and low in EHS (environment health safety) risk, raw materials are easily available, and used chemical reagents are low in toxicity and low in price, so that the synthesis process of the intermediate is a green synthesis process suitable for industrial production. In addition, the intermediate is applied to synthesis of rosuvastatin calcium and key intermediates thereof, has short route and high yield, effectively reduces the industrial production cost of rosuvastatin calcium, and has a higher industrial application prospect.

Preparation method of rosuvastatin intermediate

The invention discloses a preparation method of a rosuvastatin intermediate. The preparation method comprises the following steps: preparing a compound shown as a formula 2 into a compound shown as aformula 1 through ester formation, condensation, reduction and cyclization reactions. By the novel preparation method of the compound shown as the formula 1, the problems existing in the prior art aresolved, the product yield in a single step is increased, the product quality in the single step is improved and the production cost is greatly reduced; and the preparation method is suitable for industrialized large production.

Method for preparing 3,5-di-substituted hydroxyl-6-substituted capronate derivative

The invention discloses a method for preparing a 3,5-di-substituted hydroxyl-6-substituted capronate derivative shown as a general formula I. The method comprises a step that carboxylate shown in a general formula II and RM are subjected to a reaction under effect of a cuprous salt catalyst. The method has the advantages that the process is simple, cost is low, a catalyst with expensive price can be avoided, generation of a by-product is reduced, the post-treatment is simple, operation is easy, reaction yield is greatly increased, and the method is more suitable for large-scale industrial production.

Method for synthesizing ADA

The invention relates to a compound synthesized in the medicine field, and particularly relates to a rosuvastatin intermediate. The method for synthesizing ADA comprises the following five steps: 1, reacting S-4-chloro-3-hydroxy butyronitrile with hexamethyl-disilazane to generate an intermediate I; 2, reacting the prepared intermediate I, a reducing agent and methanesulfonic acid with tert-butyl bromoacetate to prepare an intermediate II; 3, preparing an intermediate III from the prepared intermediate II by enzyme selective reduction; 4, reacting the prepared intermediate III with acetone acetal to prepare an intermediate IV; and 5, reacting the prepared intermediate IV and tetrabutylammonium bromide with sodium acetate to prepare the target intermediate ADA. According to the method, operation for preparing ADA is more convenient; and the method has high safety coefficient and low cost, and is very suitable for industrial production.

New Statin intermediate, the preparation of the same and the preparation of Rosuvastatin using the same

The present invention provides a novel producing method for producing a core intermediate (chemical formula IV) of rosuvastatin, a novel intermediate used therefor and a producing method of rosuvastatin hemi-calcium salts using the same. The novel intermediate of the present invention can be prepared with high purity and in high yields in mild conditions, and thus the rosuvastatin intermediate and rosuvastatin hemi-calcium salts can be conveniently and efficiently mass-produced without complicated processes.

Stereoselective reduction of δ-hydroxy β-ketoesters to syndiol in achiral micellar system

A novel, efficient and stereo-selective process for synthesis of statin side chain, a key intermediate for statin type cholesterol lowering drugs such as Lipitor (atorvastatin) and Crestor (rosuvastatin) in achiral micellar media is reported. The key feature of this process is sodium borohydride reduction of δ-hydroxy β-ketoester in achiral micellar system in 92% de, thereby avoiding metal chelation methods which employ triakylborane, titanium (IV) isopropoxide or cerium (III) chloride prior to reduction.

A NOVEL, GREEN AND COST EFFECTIVE PROCESS FOR SYNTHESIS OF TERT-BUTYL (3R,5S)-6-OXO-3,5-DIHYDROXY-3,5-O-ISOPROPYLIDENE-HEXANOATE

The present invention provides a process of preparation of an intermediate useful for the preparation of statins more particularly the present invention relates to an eco-friendly and cost effective process for the preparation of tert -butyl (3R,5S)-6-oxo-3,5-dihydroxy- 3,5-O-isopropylidene-hexanoate [I].

Ru-catalyzed asymmetric hydrogenation of γ-heteroatom substituted β-keto esters

A series of enantiomerically pure γ-heteroatom substituted β-hydroxy esters were synthesized with high enantioselectivities (up to 99.1% ee) by hydrogenation of γ-heteroatom substituted β-keto esters in the presence of Ru-(S)-SunPhos catalyst. These asymmetric hydrogenations provide key building blocks for a variety of naturally occurring and biologically active compounds.

Process for the preparation of dihydroxy esters and derivatives thereof

A process is provided for the preparation of a compound of formula (1) wherein R and R′ represent optionally substituted hydrocarbyl groups and X represents a hydrocarbyl linking group. The process comprises either the stereoselective reduction of the keto group in a dihydroxy keto precursor followed by selective esterification of a primary hydroxy, or selective esterification of a primary hydroxy of a dihydroxy keto precursor followed by stereoselective reduction of the keto group.