181289-16-7

Basic information

• Product Name: Pregabalin Cyano Acid IMpurity
• Synonyms: Pregabalin Cyano Acid IMpurity;3-Cyano-5-Methylhexanoic Acid;Pregabalin Impurity 26
• CAS NO: 181289-16-7
• Molecular Formula: C₈H₁₃NO₂
• Molecular Weight: 155.19432
• Product Categories: Neurochemicals, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 181289-16-7.mol
• Article Data: 9

Chemical Properties

• Appearance: /
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Pregabalin Cyano Acid IMpurity(CAS DataBase Reference)
• NIST Chemistry Reference: Pregabalin Cyano Acid IMpurity(181289-16-7)
• EPA Substance Registry System: Pregabalin Cyano Acid IMpurity(181289-16-7)

Safety Data

• Hazardous Substances Data: 181289-16-7(Hazardous Substances Data)

Usage

Uses

3-Cyano-5-methylhexanoic Acid, a derivative of rac-Pregabalin (P704800), a GABA analogue used as an anticonvulsant.

Upstream product

• 186038-82-4 2-ethoxycarbonyl-3-cyano-5-methylhexanoic acid ethyl ester 
• 51615-30-6 diethyl 2-(3-methylbutylidene)malonate 
• 590-86-3 isovaleraldehyde 
• 724773-54-0 2-cyano-5-methylhex-2-enoic acid methyl ester 
• 61312-86-5 2-isobutyl succinonitrile 
• 1415320-54-5 3-cyano-5-methylhexanoic acid n-butyl ester 
• 1415320-53-4 3-cyano-5-methylhexanoic acid n-propyl ester 
• 181289-37-2 3-(S)-cyano-5-methyl-hexanoic acid 
• 148553-50-8 pregabilin 
• 1374689-17-4 2-cyano-2-isobutylsuccinic acid 
• 1374689-15-2 4-ethyl 1-methyl 2-cyano-2-isobutylsuccinate 
• 1350373-50-0 diethyl 2-cyano-2-isobutylsuccinate 
• 181289-17-8 (R,S)-3-cyano-5-methylhexanoic acid ethyl ester 
• 7352-02-5 ethyl 2-cyano-4-methylpentanoate 

Downstream Products

• 959760-03-3 (3S)-cyano-5-methylhexanoic acid (S)-phenyl ethyl amine salt 
• 128013-69-4 (R,S)-3-iso-butyl-4-aminobutyric acid 
• 148553-50-8 pregabilin 

Relevant articles and documents

Enzymatic production of (S)-3-cyano-5-methylhexanoic acid ethyl ester with high substrate loading by immobilized Pseudomonas cepacia lipase

(S)-3-Cyano-5-methylhexanoic acid ethyl ester is a valuable synthetic intermediate for pregabalin. Immobilized lipase PS from Pseudomonas cepacia was screened and shown to be the best biocatalyst for the enantioselective hydrolysis of 3-cyano-5-methylhexanoic acid ethyl ester, a racemic mixture involving a β-stereocenter. The optimum temperature and pH for the biocatalytic process were 35 °C and 6.0, respectively. Lipase PS IM exhibited a strong tolerance toward high substrate concentrations of up to 2.0 M (366 g/l). In the scaled-up biotransformation, (S)-3-cyano-5-methylhexanoic acid ethyl ester was produced in 0.89 M (162.9 g/l), 99.2% ee, and 44.5% yield. These results indicated that lipase PS IM catalyzed the preparation of (S)-3-cyano-5-methylhexanoic acid ethyl ester and could be used as an efficient route for the large-scale production of pregabalin.

AN IMPROVED PROCESS FOR THE PREPARATION OF PREGABALIN

The present invention relates to an improved process for the preparation of Pregabalin (I), which is simple, economical, efficient, and environment friendly, commercially viable with chemical and chiral purity at least 99.95%.

Method for synthesizing Pregabalin by taking isovaleraldehyde as raw material

The invention discloses a method for synthesizing Pregabalin by taking isovaleraldehyde as a raw material. The method comprises the steps: carrying out Knoevenagel condensation on isovaleraldehyde and diethyl malonate in a cyclohexane solvent by taking a mixture of di-n-propylamine and acetic acid as a catalyst; carrying out Michael addition on the product obtained in the step one in an alkaline alcohol solvent; carrying out deacidifying reaction on the product obtained in the step two in a solvent prepared from DMSO and water by taking lithium chloride as a catalyst under the condition of heating; carrying out hydrolytic reaction on the product obtained in the step three under alkaline conditions; carrying out catalytic hydrogenation on the product obtained in the step four by taking Raney nickel as a catalyst; and carrying out chiral resolution on the product obtained in the step five by adopting lipase Lipolase 100T. According to the method, isovaleraldehyde, which is cheap and is readily available, serves as a raw material and is subjected to Knoevenagel condensation reaction, Michael addition, decarboxylation, hydrolysis, hydrogenation reaction and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.