Process for the asymmetric synthesis of chiral indoline-2- carboxylic acids

摘要

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:PP(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;PP(b) reacting, respectively, said (S) or (R)-&agr;-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° C., in order to obtain, respectively, and (R) or (S)-&agr;-chloro-2-nitrobenzenepropanoic acid IV;P P(c) reducing the nitro group of said (R) or (S)-&agr;-chloro-2- nitrobenzenepropanoic acid (V) to an amino group; andPP(d) cyclizing the resulting (R) or (S)-&agr;-chloro-2- aminobenzenepropanoic acid in aqueous base.