SYNTHESIS AND PURIFICATION OF NATEGLINIDE

摘要

Disclosed is a method for the synthesis of [(trans-4-isopropyl cyclohexyl)-carbonyl] D-phenylalanine (nateglinide) (formula I) including the steps of (i) reacting trans-4-isopropyl cyclohexyl carboxylic acid (formula (5)) with an alkyl chloroformate (formula (13)) where R represents an alkyl group, in a ketonic solvent in the presence of a base at a temperature in the range of -20° to 30°C to form the mixed anhydride of formula (14); and (ii) reacting said mixed anhydride with an aqueous alkali salt solution of Dphenylalanine to yield a reaction mixture including [(trans-4-isopropyl cyclohexyl)carbonyl]-D-phenylalanine.