Process for the asymmetric synthesis of chiral .alpha.-hydroxy-2-nitrobenzenepropanoic acid

Abstract

Disclosed herein is a process for producing an asymmetric indoline-2-carboxylic acid of the structural Formula: ##STR1## wherein X is hydrogen, bromine, chlorine, C.sub.1-4 alkyl or C.sub.1-4 alkoxy, which comprises: (a) assymetrically reducing an o-nitrophenylpyruvic acid III by contacting the acid III with a reducing complex formed from (R)-proline or (S)-proline, respectively, and sodium borohydride in an inert solvent to form, respectively, an (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid IV; (b) reacting, respectively, said (S) or (R)-.alpha.-hydroxy-2-nitrobenzenepropanoic acid III with a Vilsmeier chlorinating reagent in which the chlorinating agent thereof is selected from a group consisting of thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride and sulfuryl chloride and the amide thereof is selected from a group consisting of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide, said reaction being run at temperatures of at least 20.degree. C., in order to obtain, respectively, and (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid IV; (c) reducing the nitro group of said (R) or (S)-.alpha.-chloro-2-nitrobenzenepropanoic acid (V) to an amino group; and (d) cyclizing the resulting (R) or (S)-.alpha.-chloro-2-aminobenzenepropanoic acid in aqueous base.

Dependencies are inferred from the claim text.