Process for the preparation of pregabalin

US10023885B2 · kind B2 · utility

Assignee

• Hikal Limited · IN

Inventors

• Swapnil Surendra Mohile · Pune, IN
• Swapnil Yerande · Ahmedabad, IN
• Sarika Madhukarrao Lunge · Pune, IN
• Rameshkumar Maghabhai Patel · Pune, IN
• Shivaji Balbhim Gugale · Pune, IN
• Rajesh Mataprasad Thakur · Pune, IN
• Ramesh Ananda Mokal · Pune, IN
• Ashok Kumar Gangopadhyay · Pune, IN
• Peter D. Nightingale · Dallas, US

Key dates

• Filing date: Nov 4, 2013
• Grant date: Jul 17, 2018
• Expiry date: Dec 3, 2033

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12P41/005
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention provides an improved process for the preparation of a compound of formula (I), which comprises the steps of: formula (I), (a) reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) optionally in presence of salts of weak acid and weak base or weak base in a suitable solvent to get 2-cyano-5-methyl-hex-2-enoic acid alkyl ester of formula (IV); (b) reacting 2-cyano-5-methyl-hex-2-enoic acid alkyl ester of formula (IV) with a suitable cyanide source in water or in an organic solvent or mixture thereof to get 2-isobutylsuccinonitrile of formula (V); (c) obtaining optionally 2-isobutylsuccinonitrile of formula (V) by reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) in presence of suitable cyanide source in water or in an organic solvent or mixture thereof in single step; (d) converting 2-isobutylsuccinonitrile of formula (V) to racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) with a genetically modified nitrilase enzyme (Nit 9N_56_2) in water or optionally with an organic co-solvent at appropriate pH and temperature; (e) converting racemic 3-cyano-5-methyl-hexanoic acid or salt thereo…