IMPROVED METHOD FOR THE PRODUCTION OF RAMIPRIL

摘要

Method for preparing ramipril (I) starting from an alkyl 3-(2-oxocyclopentyl)-2-phenylacetylamino-propionate (II). Method for preparing ramipril (I) starting from an alkyl 3-(2-oxocyclopentyl)-2-phenylacetylamino-propionate (II) comprises: (a) saponifying (II), in solution, by treatment with acid or base to produce free acid (III); (b1) reacting (III) to a mixture of (IV) and (V), or their salts, by treatment with penicillin-G amidase (PGA) or (b2) reacting (II) with PGA then treating the product with acid or base, to form the mixture of (IV) and (V); (c) converting (V), or salt, to (VI), or salt, by catalytic hydrogenation; and (d) reacting (VI) with (VII) to give (I); or reacting (VI) with benzyl alcohol to form benzyl ester (VIII), then reacting (VIII) and (VII) to give (X); or reacting (VIII) with (IX), forming (X), then catalytic hydrogenation of (X) to (I). R : 1-4C alkyl Independent claims are included for the following: (1) methods for preparing a mixture of (IV) and (V), as described; and (2) (II), (III) and the mixture of (IV) and (V), or salts, as new compounds . [Image] [Image] [Image] [Image] ACTIVITY : Hypotensive. No details of tests for hypotensive activity are given. MECHANISM OF ACTION : Inhibiting angiotensin-converting enzyme.