To obtain the subject compound having a high quality by subjecting a specific substrate compound to a hydrolysis reaction under specific conditions to release the RCO group, and subsequently isolating the product, while inhibiting the by-production of impurities difficult in their purification and removal.
This method for producing the captopril of formula II comprises subjecting a substrate compound of formula I (R is an alkyl, an alkoxy) to a hydrolysis reaction in the presence of a strong acid (preferably hydrochloric acid) in an aqueous medium under conditions comprising a pH of ≤1 and a temperature of ≥40°C (preferably 50-100°C) and subsequently isolating the RCO group-released product. The strong acid is preferably used in an amount of ≥0.1 time molar equivalent, preferably approximately 0.2-2 times equivalent that of the compound of formula I. The substrate compound of formula I includes N-(D-α-methyl-β-acethylthiopropionyl)-L-proline. The captopril useful as an antihypertensive medicine can thereby be obtained in a high yield and at a low cost.
KANO FUMIHIKO
OOKUBO TAKAHIRO
UEDA YASUYOSHI
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