125988-01-4

Usage

Uses

Used in Pharmaceutical Industry:
(5R)-6-Cyano-5-hydroxy-3-oxo-hexanoic Acid tert-Butyl Ester is used as an intermediate in the preparation of Atorvastatin 10-Trans (Atorvastatin Impurity AT10) for the pharmaceutical industry. It plays a crucial role in the synthesis of Atorvastatin, a widely prescribed medication for lowering cholesterol levels and managing cardiovascular diseases. Its unique chemical properties contribute to the development of this important drug.

Upstream product

• 125971-92-8 (R)-1,1-dimethylethyl 6-cyano-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3oxohexanoate 
• 104197-11-7 magnesium salt of tert-butyl hydrogen malonate 
• 540-88-5 acetic acid tert-butyl ester 
• 141942-85-0 (R)-ethyl 4-cyano-3-hydroxybutyrate 
• 143-33-9 sodium cyanide 
• 404958-08-3 tert-butyl (R)-6-chloro-5-hydroxy-3-oxohexanoate 
• 141942-83-8 (R)-3-(tert-Butyl-dimethyl-silanyloxy)-4-cyano-butyric acid butyl ester 
• 141942-82-7 (R)-(-)-ethyl 4-cyano-3-(tert-butyldimethylsilyloxy)butyrate 
• 105876-27-5 (R)-4-cyano-3-hydroxybutanoic acid methyl ester 
• 150942-98-6 t-butyl lithioacetate 
• 141942-86-1 n-butyl (R)-(-)-4-cyano-3-hydroxybutyrate 
• 141942-84-9 (R)-methyl (3-hydroxy-4-cyano)-butanoate 
• 477541-55-2 (R)-3-(tert-Butyl-dimethyl-silanyloxy)-5-imidazol-1-yl-5-oxo-pentanenitrile 

Downstream Products

• 125971-93-9 (3R,5R)-tert-butyl-6-cyano-3,5-dihydroxyhexanoate 
• 247592-53-6 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate 
• 186508-94-1 (3S,5R)-tert-butyl 6-cyano-3,5-dihydroxyhexanoate 
• 125971-94-0 2-((4R, 6R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid tert-butyl ester 

Relevant academic research and scientific papers

FUSED TRICYCLIC KRAS INHIBITORS

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.

Preparation method of (R)-6-cyan-5-hydroxy-3-tert-butyl carbonyl hexanoate

The invention discloses a preparation method of (R)-6-cyan-5-hydroxy-3-tert-butyl carbonyl hexanoate. The preparation method comprises the following steps: under the protection of nitrogen, adding tert-butyl acetate and 1,8-diazabicyclo-undecenoic-7-alkene into 2-methyltetrahydrofuran to prepare a solution A; dissolving (R)-4-cyan-3-ethyl hydroxybutyrate into 2-methyltetrahydrofuran to obtain a solution B; adding the solution A and the solution B into a small amount of 2-methyltetrahydrofuran dropwise, controlling the reaction temperature to be 20 to 30 DEG C, and performing stirring reactionfor 1 to 5 hours after adding the solution A and the solution B dropwise and simultaneously; adding water into the reaction system dropwise, standing and layering; performing reduced-pressure concentration on organic phase to obtain the (R)-6-cyan-5-hydroxy-3-tert-butyl carbonyl hexanoate, recovering a solvent simultaneously, and concentrating aqueous phase to recover the 1,8-diazabicyclo-undecenoic-7-alkene. According to the preparation method, low-temperature liquid nitrogen is not needed, energy consumption is low, dangerous reagents such as metal lithium and sodium are not used, the process is safe, the solvent and the reagents can be recovered after reaction, and environmental friendliness is achieved.

PROCESS FOR CROSSED CLAISEN CONDENSATION REACTIONS PROMOTED BY LITHIUM AMIDE IN LIQUID AMMONIA

The present invention provides a use of lithium amide in liquid ammonia as a base to produce an enolate from at least one ester starting material in a crossed Claisen condensation reaction, wherein at least one ester starting material is a β-hydroxy ester. Also provided is a method of producing lithium amide in situ for use in a crossed Claisen condensation reaction, wherein lithium is added to liquid ammonia, followed by an electron transfer agent, as well as a method of carrying out a crossed Claisen condensation reaction using an ester starting material and a β-hydroxy ester, using lithium amide in liquid ammonia produced in situ.

PROCESS FOR CROSSED CLAISEN CONDENSATION REACTIONS PROMOTED BY LITHIUM AMIDE IN LIQUID AMMONIA

The present invention provides a use of Iithium amide in liquid ammonia as a base to produce an enolate from at least one ester starting material in a crossed Claisen condensation reaction, wherein at least one ester starting material is a β-hydroxy ester. Also provided is a method of producing lithium amide in situ for use in a crossed Claisen condensation reaction, wherein lithium is added to liquid ammonia, followed by an electron transfer agent, as well as a method of carrying out a crossed Claisen condensation reaction using an ester starting material and a β-hydroxy ester, using lithium amide in liquid ammonia produced in situ.

CONTINUOUS PROCESS FOR THE PRODUCTION OF BETA-KETO ESTERS BY CLAISEN CONDENSATION

The invention concerns a continuous process for the production of compounds having the general formula (6) comprising providing to a reaction zone a continuous stream of an alkyl acetate and a continuous stream of an alkali metal or alkaline earth metal amide base and contacting the continuous streams together in the reaction zone to yield an enolate compound, providing to the or a separate reaction zone a continuous stream of a compound of formula (5) and contacting the continuous stream of compound (5) with a continuous stream of the enolate in the or the separate reaction zone at a temperature above 20°C to yield an intermediate compound and treating the intermediate compound of formula (1) with an acid to yield the compound of formula (6).

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.

COMPOSITIONS AND METHODS FOR PRODUCING STEREOISOMERICALLY PURE STATINS AND SYNTHETIC INTERMEDIATES THEREFOR

The present disclosure provides ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, method of using the engineered ketoreductase enzymes to synthesize a variety of chirally pure compounds, and the chirally pure compounds prepared therewith.

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.

ENZYMATIC PROCESSES FOR THE PRODUCTION OF 4-SUBSTITUTED 3-HYDROXYBUTYRIC ACID DERIVATIVES AND VICINAL CYANO, HYDROXY SUBSTITUTED CARBOXYLIC ACID ESTERS

The present invention provides methods and composition for preparing 4-substituted 3-hydroxybutyric acid derivatives by halohydrin dehalogenase-catalyzed conversion of 4-halo-3-hydroxybutyric acid derivatives. The present invention further provides methods and compositions for preparing 4-halo-3-hydroxybutyric acid derivatives by ketoreductase-catalyzed conversion of 4-halo-3ketobutyric acid derivatives. The present invention also provides methods and compositions for preparing vicinal cyano, hydroxyl substituted carboxylic acid esters.