A PROCESS FOR THE PREPARATION OF ZOFENOPRIL CALCIUM SALT

摘要

A process for the preparation of polymorph A of zofenopril calcium salt in substantially pure form, which comprises: a) reaction of S(-)-3-benzoylthio- 2- methylpropanoic acid chloride with cis-4-phenylthio-L-proline in water at pH ranging from 9.0 to 9.5 and recovery of zofenopril in the acidic form; b) salification of acid zofenopril with a potassium salt in alcoholic solution, and recovery of the resulting potassium salt; c) conversion of the potassium salt to the calcium salt by addition of a zofenopril potassium salt aqueous solution to a CaCl2 aqueous solution at a temperature of 70-90 ~C with simultaneous seeding to promote the precipitation of polymorph A.