Process for the manufacture of (S)-3-amino-1-substituted-pyrrolidines
AssigneeWarner-Lambert Company
InventorsTung Van Le, F. Gregory Spence, James N. Wemple
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Abstract
A novel process for preparing a stereospecific (S)-3-amino-1-substituted pyrrolidine used as a key intermediate in preparing quinolone and naphthyridone antibacterial agents where the 7-position is occupied with a sterospecific 3-amino-pyrrolidine side chain is described starting from inexpensive L-aspartic acid. L-aspartic acid is converted to the desired (S)-3-aminopyrrolidine via a novel, high yield transformation of a substituted aziridine.
Claims8
A process for the preparation of an (S)-3-amino-1-substituted pyrrolidine of the formula ##STR5## wherein R' is benzyl, benzyl substituted by lower alkyl or lower alkoxy, or benzhydryl, which comprises:
- (1) blocking the amino group of L-aspartic acid with an alkyl or arylsulfonyl blocking group;
- (2) reducing the N-blocked-L-aspartic acid, or di-lower alkyl-ester thereof with a hydride reducing agent;
- (3) reacting the N-blocked-1,4-butanediol with about two equivalents of a thionyl halide or an alkyl or arylsulfonyloxy halide in the presence of about three equivalents of a base to form a compound of the formula ##STR6## wherein L is halo or alkyl- or arylsulfonyloxy and R is an alkyl or arylsulfonyl group;
- (4) reacting the product of step (3) with R'-NH.sub.2 in the presence of a tertiary amine to form a 1-R'-3-(blocked amino) pyrrolidine in which R' is as defined above, and
- (5) removing the blocking group by hydrolysis or reduction to afford the desired product.
Dependencies are inferred from the claim text.