Verfahren zur Herstellung von Estern des 3-Phenyl-3-hydroxypyrrolidins und deren Salzen

摘要

The invention comprises compounds of the general formula: and acid addition salts thereof, wherein R is a hydrogen atom or a fatty acid acyl radical containing not more than six carbon atoms, R1 is a hydrogen atom or an alkyl or alkenyl group containing not more than four carbon atoms or a phenylalkyl or phenylalkenyl group and R2 R3 R4 and R5 represent hydrogen or alkyl radicals containing not more than four carbon atoms and the preparation thereof (1) (wherein R1 is other than a hydrogen atom) by (a) reacting a reactive phenylmetallo compound under anhydrous conditions with a 3-pynolidone of the formula: (wherein "hydro carbon" has the same meaning as R1, but does not include a hydrogen atom), decomposing the product with an aqueous medium, and, if desired, converting the product to the free base or an acid addition salt thereof, further, if desired, reacting the product or a reactive derivative thereof with an appropriate fatty acid or a reactive derivative thereof to form the ester, optionally converting this to the base of acid addition salt; or (b) by introducing the "hydro carbon radical" on the amino nitrogen atom of a compound of formula (I) wherein R1 is a hydrogen atom; and (2) (wherein R1 is a hydrogen atom) by catalytically reducing an appropriate compound of formula (I) wherein R1 is a benzyl group, if desired converting the product into a base or an acid addition salt. The 3-pyrrolidones of formula (II) are prepared by (a) cyclization, in the presence of a condensing agent, of a diester of the general formula: wherein R6 and R7 are organic radicals, followed by hydrolytic decarboxylation of the 2- or 4-carboxylate group; (b) by the reaction of a dihalide of the general formula: in which the carbonyl group may be protected such as by conversion into a hydroxymethylene group, with an amine R1 NH2, followed by regeneration of the carbonyl group if necessary; and (c) cyclization, in the presence of a condensing agent, of a dinitrile of the general formula: followed by hydrolysis of the resulting aminonitrile. The starting materials may be used in their optically active or racemic forms, the racemates if desired being resolved by fractional crystallisation of a salt or an ester formed with an optically active acid. The Provisional Specification discloses compounds of the general formulae: where R represents hydrogen or a lower fatty acyl radical, R1 represents hydrogen, a lower alkyl radical, a benzyl or a phenethyl radical and R2, R3, R4, R5, R6 and R7 are the same or different and represent hydrogen or lower alkyl.