Enantioselective Synthesis of alpha,alpha-Disubstituted Amino Acid Derivatives via Enzymatic Resolution: Preparation of a Thiazolyl-Substituted alpha-Methyl alpha-Benzyl Amine.
A new and efficient enantioselective synthesis of the (S)-alpha,alpha-disubstituted phenethylamine 1 via Lipase resolution of the esters 3 and 4 is described. The effect of pH, enzyme load, and solubilizing additives has been studied and optimized. Conversion of the carboxylic acid 10 to the desired thiazole 1 is accomplished in high overall yield via an intermediate oxazolinone 13. This facile process requires only a single chromatographic step, and multigram quantities of 1 have been prepared.
Spero
Denice M.
DM
Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368 Ridgefield, Connecticut 06877.
Kapadia
Suresh R.
SR