The invention provides a method for preparing zofenopril
calcium. N-acetyl-L-oxyproline is adopted as a
raw material. The method includes: a step of subjecting the N-acetyl-L-oxyproline and
methanol to esterification, subjecting the obtained product and paratoluensulfonyl
chloride to sulfonation, and subjecting the obtained product and
thiophenol prepared from a
sodium thiophenolate solution to thiophenyl substitution; a step of hydrolyzing the obtained product into an
free acid by utilization of an alkali, performing recrystallization for purification, and performing deacetylation with
hydrochloric acid to obtain (cis)-4-thiophenyl-L-
proline hydrochloride; a step of reacting (S)-3-(benzoyl sulfhydryl)-2-methylpropanoic acid with
thionyl chloride to obtain (S)-3-(benzoyl sulfhydryl)-2-methyl propionylchloride; a step of reacting the (S)-3-(benzoyl sulfhydryl)-2-methyl propionylchloride with the (cis)-4-thiophenyl-L-
proline hydrochloride to obtain the
free acid zofenopril; and a step of forming a
potassium salt, purifying and reacting with a
calcium chloride to obtain a
calcium salt, thus obtaining a final product zofenopril calcium. The method has characteristics of easily available raw materials, simple preparation method, mild conditions, easy control, reasonable monitoring points in the preparation process, effective removal and control of impurities, capability of producing the final product with the needed
crystal form preferentially in a
high ratio, suitability for industrial production and large application value.