196085-84-4

Basic information

• Product Name: (4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate
• Synonyms: (4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate;tert-Butyl 2-((4R,6S)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate;Atorvastatin Impurity 19
• CAS NO: 196085-84-4
• Molecular Formula: C14H23NO4
• Molecular Weight: 269.33672
• Mol File: 196085-84-4.mol

Chemical Properties

• Boiling Point: 364.1±17.0 °C(Predicted)
• Appearance: /
• Density: 1.016±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• CAS DataBase Reference: (4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: (4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate(196085-84-4)
• EPA Substance Registry System: (4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate(196085-84-4)

Safety Data

• Hazardous Substances Data: 196085-84-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(4R,6S)-tert-Butyl-6-cyanoMethyl-2,2-diMethyl-1,3-dioxane-4-acetate is used as an impurity in the synthesis of Atorvastatin (A791750) for the pharmaceutical industry. Atorvastatin is a selective, competitive HMG-CoA reductase inhibitor, specifically indicated for lowering both elevated LDL-cholesterol and triglycerides in patients with hypercholesterolemia. The presence of this compound as an impurity is crucial for the development and production of Atorvastatin, ensuring the effectiveness and safety of the drug for treating hypercholesterolemia.

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 
• 477541-55-2 (R)-3-(tert-Butyl-dimethyl-silanyloxy)-5-imidazol-1-yl-5-oxo-pentanenitrile 
• 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 
• 74530-57-7 tert-butyl 4-bromoacetoacetate 
• 144-55-8 sodium hydrogencarbonate 
• 77-76-9 2,2-dimethoxy-propane 
• 1105067-92-2 tert-butyl (3S,5S)-6-cyano-3,5-dihydroxyhexanoate 

Relevant articles and documents

An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis

An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for the synthesis of an effective HMG-CoA reductase inhibitor atorvastatin, is described. The synthesis is based on the iodolactonization of hepta-1,6-dien-4-ol to 4-allyl-6-iodomethyl-1,3-dioxan-2-one, which was converted in several steps to (6-allyl-2,2-dimethyl-1,3-dioxan-4-yl)-acetonitrile. This intermediate provided (6-cyanomethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid either via the corresponding aldehyde or via (2,2-dimethyl-6-oxiranylmethyl-1,3-dioxan-4-yl)acetonitrile.

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.

A atorvastatin condensation the intermediate product of the resolution method (by machine translation)

The invention relates to a kind of atorvastatin "condensate" intermediate resolution method, the method, comprises the following steps: step 1, takes shrinks compound trans-isomer mixture, in order to isopropanol as the solvent heating and dissolves it, s

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.

Preparation method of 3,5,6-substitued caproate derivative

The invention discloses a preparation method of a 3,5,6-substitued caproate derivative which is represented as the general formula (I), wherein the method is prepared with lactone as a raw material and an iodinated substance as an intermediate. The method is low in raw material cost, employs simple reactions, is stable and is high in yield, is easy to control and is suitable for large-scale 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.

Synthesis of some impurities and/or degradation products of atorvastatin

Synthesis of some impurities and/or degradation products of atorvastatin, calcium (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl) pyrrol-1-yl]-3,5-dihydroxyheptanoate, is described. These include its desfluoro analog, the corresponding (3S,5S)-and (3S,5R)-epimers, atorvastatin lactone, and some other potential impurities. The synthesized compounds as well as the corresponding intermediates were characterized by 1H NMR, 13C NMR and MS.