Patent ID: 9150499
Filing Date: 2015-10-06
Classification: A61P,C07C

Abstract:
1. A process for preparing nateglinide of formula (I) or a pharmaceutically-acceptable salt thereof, wherein the nateglinide is polymorphic Form B, which process comprises: preparing (−)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester of formula (II) by condensation of a D-phenylalanine alkyl ester of formula (IV) or an acid addition salt thereof with trans-4-isopropyl-cyclohexylcarboxylic acid of formula (III) in the presence of a condensation solvent, an alkali metal hydroxide and a condensing agent to form a (−)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester of formula (II) without intermediate conversion to an acid chloride or an N-hydroxysuccinmide ester, of formula (III) wherein the Alk group is a C hydrolysis of compound (II) in the presence of a hydrolysis solvent, wherein the hydrolysis solvent is a mixture of a ketone and water, and the ketone:water ratio varies from 5:1 to 1:1 v/v; and optionally conversion of the nateglinide (I) to a salt thereof.