Process for the preparation of nateglinide, preferably in B-form

A process for the preparation of nateglinide comprising the following steps:

• i) reaction in a first organic solvent between D-phenylalanine methyl ester or a salt thereof, trans 4-isopropylcyclohexancarboxylic acid and an acyl chloride or carbonyldiimidazol, to obtain the nateglinide methylester;
• ia) optionally isolating the nateglinide methylester thus obtained and re-dissolving the nateglinide methylester in a second organic solvent, to give a solution,
• ii) addition of water and alkali hydroxide to the reaction mixture coming from step i) without isolating the nateglinide methyl ester, or, if applicable, to the solution of step ia), and separation of the aqueous phase containing the alkali salt of nateglinide;
• iii) addition of hydrochloric acid to the aqueous phase coming from step ii), to obtain nateglinide,
• wherein the organic solvent actually employed in step ii) is a solvent non-miscible with water.