125971-94-0

Basic information

• Product Name: (4R,6R)-tert-Butyl-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate
• Synonyms: ATS-8;(4R,6R)-T-BUTYL-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXANE-4-ACETATE;(4R,6R)-TERT-BUTYL-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXANE-4-ACETATE;(4R,CIS)-1,1-DIMETHYLETHYL-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXANE-4-ACETATE;(4R,3R)-TERT-BUTYL-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXANE-4-ACETATE;tert-Butyl (4R,3R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate;TERT-BUTYL[(4R,6R)-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXAN-4-YL]ACETATE;(4R-CIS)-1,1-DIMETHYLETHYL-6-CYANOMETHYL-2,2-DIMETHYL-1,3-DIOXANE-4-ACETATE (ATS-8)
• CAS NO: 125971-94-0
• Molecular Formula: C₁₄H₂₃NO₄
• Molecular Weight: 269.34
• EINECS: 425-780-3
• Product Categories: Chemical intermediate for Atorvastatin Calcium;INTERMEDIATESOFATORVASTATIN;chiral;(intermediate of atorvastatin);Chiral Building Blocks;Cyanides/Nitriles;Organic Building Blocks;Atorvastatin intermediates
• Mol File: 125971-94-0.mol

Chemical Properties

• Melting Point: 65-69 °C(lit.)
• Boiling Point: 364.1 °C at 760 mmHg
• Flash Point: 159.2 °C
• Appearance: white to light yellow crystal powder
• Density: 1.016 g/cm³
• Vapor Pressure: 1.73E-05mmHg at 25°C
• Refractive Index: 1.439
• Storage Temp.: 2-8°C
• Solubility: soluble in Chloroform
• CAS DataBase Reference: (4R,6R)-tert-Butyl-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: (4R,6R)-tert-Butyl-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate(125971-94-0)
• EPA Substance Registry System: (4R,6R)-tert-Butyl-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate(125971-94-0)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 125971-94-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(4R,6R)-tert-Butyl-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate is used as an intermediate in the synthesis of Atorvastatin, a selective and competitive HMG-CoA reductase inhibitor. Atorvastatin is specifically indicated for lowering both elevated LDL-cholesterol and triglycerides in patients with hypercholesterolemia. Its role as an intermediate in the production of Atorvastatin makes it a crucial component in the development and manufacturing of this cholesterol-lowering drug.

InChI:InChI=1/C14H23NO4/c1-13(2,3)19-12(16)9-11-8-10(6-7-15)17-14(4,5)18-11/h10-11H,6,8-9H2,1-5H3/t10-,11-/m1/s1

Upstream product

• 143-33-9 sodium cyanide 
• 141942-87-2 [(4R,6S)-6-(4-Chloro-benzenesulfonyloxymethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-acetic acid tert-butyl ester 
• 141942-88-3 [(4R,6S)-6-(4-Bromo-benzenesulfonyloxymethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-acetic acid tert-butyl ester 
• 141942-89-4 tert-butyl 2-[(4R,6S)-2,2-dimethyl-6-[(4-nitrophenylsulfonyloxy)methyl]-1,3-dioxan-4-yl]acetate 
• 150942-98-6 t-butyl lithioacetate 
• 141942-82-7 (R)-(-)-ethyl 4-cyano-3-(tert-butyldimethylsilyloxy)butyrate 
• 477541-55-2 (R)-3-(tert-Butyl-dimethyl-silanyloxy)-5-imidazol-1-yl-5-oxo-pentanenitrile 
• 773837-37-9 sodium cyanide 
• 154026-94-5 (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester 
• 791115-48-5 ((4R,6R)-6-cyanomethyl-2,2-dimethyl-[1,3]-dioxan-4-yl)-acetic acid chloride 
• 75-65-0 tert-butyl alcohol 
• 125971-93-9 (3R,5R)-tert-butyl-6-cyano-3,5-dihydroxyhexanoate 
• 848644-99-5 (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate 
• 7397-46-8 diethyl methoxy borane 

Downstream Products

• 125971-86-0 tert-butyl [(4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate 
• 134523-01-6 atorvastatin sodium 
• 134395-00-9 (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid t-butyl ester 
• 125971-95-1 tert-butyl (4R,6R)-6-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]ethyl}-2,2-dimethyl-1,3-dioxane-4-acetate 
• 134523-03-8 lipitor 

Relevant articles and documents

Atorvastatin calcium intermediate as well as preparation method and application thereof

The invention discloses an atorvastatin calcium intermediate as well as a preparation method and application thereof. A synthesis process of the intermediate is environmentally-friendly, simple to operate and low in EHS risk; raw materials are easy to obtain; a used chemical reagent is small in toxicity and low in cost; and the synthesis process is a green synthesis process suitable for the industrial production. Moreover, the intermediate provided by the invention is applied to the synthesis of atorvastatin calcium and a key intermediate thereof, the route is relatively short, the yield is high, the industrial production cost of the atorvastatin calcium is effectively reduced, and the atorvastatin calcium intermediate has a relatively high industrial application prospect.

Preparation method of atorvastatin calcium intermediate

The invention belongs to the technical field of pharmaceutical chemistry and in particular relates to a preparation method of an atorvastatin calcium intermediate. According to the preparation methodprovided by the invention, an intermediate compound II is used as a starting material and the starting material is transformed into a lithium reagent compound III and an aldehyde group compound IV step by step; then the lithium reagent compound III and the aldehyde group compound IV react with hydroxylamine to generate an oxime compound V; an oxime group is dehydrated to obtain cyano I-A; and thenprotection is carried out to obtain a target compound I. Compared with an existing report, the route effectively avoids the utilization of highly toxic substances including sodium cyanide and hydrocyanic acid; and reactions in the whole route are common, conditions are moderate and the yield is relatively good. The preparation method provided by the invention is more beneficial to large-scale industrial production of the intermediate I.

Preparation method of atorvastatin calcium intermediate

The invention belongs to the field of medicines and chemical industry, and particularly relates to the field of pharmacy, in particular to a preparation method of an atorvastatin calcium intermediate.The preparation method comprises the following steps: firstly preparing a compound II into a lithium reagent, then reacting with methyl chloroformate, introducing an ester group, aminolyzing the ester group into amine, dehydrating the amide, and finally reducing a cyano group to obtain a target compound. By the brand-new preparation method of the atorvastatin calcium intermediate, a compound VI can be synthesized under the premise that highly toxic substances such as hydrocyanic acid, hydrobromide and the like are not used, and the compound VI is used for preparing a compound I; reagents usedin the whole preparation process are safe and environment-friendly, and the preparation method is more suitable for industrial production.

Atorvastatin calcium side chain intermediate preparation method

The present invention provides an atorvastatin calcium side chain intermediate preparation method comprising the following steps: (1) a compound II is added into 2,2-dimethoxypropane liquid, the molar ratio of compound II to 2,2-dimethoxypropane is 1: 2.2 to 13.2; (2) an acidic resin catalyst with the mass accounting for 2.6 to 9.5% of the mass of the compound II is added, and at 10-30DEG C, the mixture is stirred for reaction for 4-6 hours; and (3) the reaction system is filtered, filtrate is concentrated to obtain an oil matter, and the oil matter is recrystallized to obtain a solid atorvastatin calcium side chain intermediate I. By the method, the solid atorvastatin calcium side chain intermediate I with the purity of more than 99% is obtained, and the yield is greater than 95%. The reaction conditions are mild, decolorization treatment is not required, production cost is low, the reaction is stable and easy to control, safety is high, operation is easy, the catalyst and the reactant 2,2-dimethoxypropane are recyclable, waste liquids and waste residues are not produced, and the method is green and environmentally-friendly.

2 - ((4R, 6R) - 6-aminomethyl-ethyl -2,2-dimethyl -1,3-dioxane-4-yl) acetate simple method for preparing

The invention relates to a simple preparation method of 2-((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxyhexacyclo-4-yl)acetate (I). The method comprises the following steps: reacting 3-cyanopropylene (II) and 3,3-dialkoxypropionate (III) or 3-alkoxyacrylate (IV) under the catalytic action of Lewis acid to prepare 2-((4R,6R)-6-cyanomethyl-2-ester-methyl-1,3-dioxyhexacyclo-4-yl)acetate (V), removing the solvent, directly carrying out blocking group conversion to prepare 2-((4R,6R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxyhexacyclo-4-yl)acetate (VI), and carrying out Raney nickel catalytic hydrogenation two-step reaction to prepare (I). The stable form of the hexatomic ring chair-structure equatorial bond is utilized to construct the chiral center without using any additional chiral assistant. The method has the advantages of accessible raw materials, short reaction procedure and low cost, avoids carbonyl asymmetric reduction, is simple and environment-friendly, and is industrial production.

PROCESS FOR THE PRODUCTION OF ATORVASTATIN CALCIUM IN AMORPHOUS FORM

A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.

Process for the production of atorvastatin calcium un amorphous form

A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.

Process for the production of atorvastatin calcium in amorphous form

A process for the production of amorphous atorvastatin calcium and stabilized, amorphous atorvastatin calcium is provided.

CRYSTALLINE FORM OF ATORVASTATIN HEMI CALCIUM

The present invention relates to novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof useful as pharmaceutical agents, to methods for their production and isolation, to pharmaceutical compositions which include novel crystalline form R of atorvastatin hemi calcium salt and hydrates thereof and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment.

PROCESS FOT THE PREPARATION OF (4-HYDROXY-6-OXO-TETRAHYDROPYRAN-2-YL) ACETONITRILE AND DERIVATIVES THEREOF

The invention relates to a process for the preparation of (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile from 6-X-substituted-methyl-4-hydroxy-tetrahydro-pyran-2-one, wherein X stands for a leaving group, by reacting 6-X-substituted-methyl-4-hydroxy-tetrahydro-pyran-2-one with a cyanide ion in water and by subsequent lowering of the pH to a pH between 0 and 5. (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile and other compounds obtainable from (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile may suitably be used in the preparation of a pharmaceutical preparation, more in particular in the preparation of statins, more in particular in the preparation of Atorvastatine or a salt thereof, for instance its calcium salt. The invention also relates to (4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-acetonitrile and other compounds obtainable therefrom.