A process is disclosed for obtaining manipulated proportions of the (+) and (-) enantiomers of [(6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-2-phenyl-1H-inden-5-yl)oxy]aceti c acid by asymmetric chiral phase transfer catalysis.
This is a continuation of Ser. No. 07/547,537 filed June 29, 1990, now abandoned, which is a continuation of Ser. No. 07/366,261 filed June 12, 1989, now abandoned which is a continuation of Ser. No. 07/246,908 filed Sept. 16, 1988, now abandoned which is a continuation of Ser. No. 07/060,947 filed June 15, 1987, now abandoned, which is a continuation of Ser. No. 06/752,324 filed July 5, 1985, now abandoned which is a diversion of Ser. No. 06/579,341, filed Feb. 17, 1984, now U.S. Pat. No. 4,578,509 which is a continuation-in-part of Ser. No. 06/481,200, filed Apr. 1, 1983, now abandoned.
This invention relates to an optically active hydroquinine (amino-3 phenyl)-1 ethanesulfonate (form A), preparation thereof and its use as an intermediate in the preparation of cholecystokinine and gastrin antagonists.
A process for the stereoselective synthesis of [R]- and [S]-2,3-dihydro-1,3-dimethyl-2-oxo-1H-indole-3-acetonitriles comprises reacting racemic and 5-alkoxy-substituted (.+-.)-1,3-dimethyloxindoles with a halogenated acetonitrile in the presence of a substituted N-benzyl cinchoninium, quinidinium, cinchonidinium, or quininium catalyst. The resulting alkylated oxindoles can be converted to primary amines by catalytic reduction in the presence of hydrogen gas. One of the primary amines, such as enantiomers of 3-(2-aminoethyl)-1,3-dihydro-1,3-dimethyl-5-methoxy-2H-indol-2-one, can be enriched by contact with a chiral tartaric acid in an amount sufficient to preferentially precipitate a salt of the chiral acid and one of the enantiomers. The product can be used in the synthesis of stereospecific forms of physostigmine and related compounds having pharmaceutical activity.
