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: 1) 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 poyassium salt in alcoholic solution, and recovery of the resulting potassium salt; c) conversion of the potassium salt to the calcium salt by addition of 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.