US 5,347,017 A · Process for chiral 3-(1-amino-1,1-bisalkylmethyl)-1-substituted-pyrrolidines

Abstract

The process for the preparation of chiral 3-(1-amino-1,1-bisalkylmethyl)-1-substituted-pyrrolidines used as key intermediates for the preparation of naphthyridine and quinolone antibacterial agents which comprises reacting readily available chiral 1-substituted-3-pyrrolidinols to their corresponding chiral sulfonate esters; converting the sulfonate esters to chiral 1-substituted-3-cyanopyrrolidines having an inverse configuration, and then dialkylating the chiral cyanopyrrolidines with alkyl lithium in the presence of a Lewis acid without racemization at the asymmetric carbon atom is described.

Claims28

Dependent claims

A process for preparing a chiral compound of the formula ##STR5## in which * denotes an asymmetric carbon atom having the R or S configuration;

R' is benzyl, p-methoxybenzyl, .alpha.-methylbenzyl or an optical isomer thereof, methoxy, ethoxy, or dimethylamino, and R is alkyl of 1 to 3 carbon atoms, which comprises:
(1) reacting a chiral 1-R'-3-pyrrolidinol with an alkylsulfonyl halide or arylsulfonyl halide in the presence of a base in an aprotic solvent;
(2) reacting a resulting chiral 1-R'-3-pyrrolidinol sulfonate ester with a cyanide reagent in an aprotic solvent, and
(3) reacting a resulting chiral 3-cyanopyrrolidine of opposite configuration with an excess of alkyl lithium in the presence of a Lewis acid in an aprotic solvent.

1 more element

Dependencies are inferred from the claim text.

Process for chiral 3-(1-amino-1,1-bisalkylmethyl)-1-substituted-pyrrolidines

Life of this patent

Process for chiral 3-(1-amino-1,1-bisalkylmethyl)-1-substituted-pyrrolidines

Life of this patent

Abstract

Claims28