PROCESS FOR PREPARING LEVETIRACETAM AND RACEMIZATION OF (R)- AND (S)-2-AMINO BUTYNAMIDE AND THE CORRESPONDING ACID DERIVATIVES

摘要

Process for the preparation of (S)-(-)-alpha--ethyl-2-oxo-1-pyrrolidineacetamide of Formula (I), comprising the steps of (i) resolution of racemic 2-amino butyramide with L-(+)-tartaric acid either in alcoholic solvents like methanol, isopropanol, ethanol or in water or mixture of water-alcohol to provide (S)-(+)-2-amino butyramide tartarate salt; and ii)direct conversion of (S)-(+)-2-amino butyramide tartarate salt and 4-halobutryl chloride in presence of inorganic or organic base in suitable solvent and drying agents yielded the desired (S)-(-)-alpha--ethyl-2-oxo-1-pyrrolidineacetamide (I). Further (S)-(+)-2-aminlo butyramide tartarate salt is converted to (S)-(+)-2-amino butyramide hydrochloride salt, by reacting with an inorganic or organic base in a suitable solvent followed by reaction with HCl gas in an appropriate solvent. The preparation of (S)-(+)-2-amino butyramide hydrochloride salt, which is an intermediate for Levetiracetam, is prepared from (S)-(+)-2-amino butyramide tartarate salt in presence of inorganic base selected from potassium carbonate or hydroxide, sodium carbonate or hydroxide, ammonia gas, and organic base selected from triethyl amine, DMAP, and the like and a suitable solvent selected from methanol, isopropanol, ethanol or in water or mixture of water-alcohol.