Study Of The Preparation Of(S)-a-Ethyl-2-OXO-1-Pyrrolidineacetamide

(S)-a-ethyl-2-oxo-1-pyrroiidineacetamide is first prepared by UCB company, and is known to be useful as an agent for the treatment or prevention of epilepsy and other neurological disorders. In our work, we investigated it’s preparation which was suitable for scaled produce, using a-amino butyric acid as original material, High optical pure (S)-a-ethyl-2-oxo-l-pyrrolidineacetamide was obtained and the reaction of each step was optimized.Process of the preparation of (S)-a-ethyl-2-oxo-l-pyrrolidineacetamide included1)Using racemic a-amino butyric acid as original material, methyl a-amino butyrate hydrochloric salt was obtained by esterification,2)Methyl a-amino butyrate was obtained by the processing of dehydrochloric acid from methyl a-amino butyrate hydrochloric salt,3)a-amino butylamide was obtained by aminolysis,4)Optical pure intermediate (S)-(+)-a-amino butylamide was obtained by resolution of a-amino butylamide with L-(+)-tartaric and then was debased in the presence of inorganic base,5) Conversion of (S)-(+)-a-amino butylamide and4-halobutryl chloride in presence of inorganic or organic base in suitable solvent and drying agents yielded the desired (S)-a-ethyl-2-oxo-l-pyrrolidineacetamide.All synthe-sized products and intermediates analyzed by IR、1H-NMR and HPLC.The process of dehydrochloric acid was carried out using chloroform as solvent, by which the hydrolysis reaction was controlled. The method of different aminolysis was compared. It was found that by adding alkali agent as catalyst can improve the yield of aminolysis remarkably. The best aminolysis reaction time was obtained by TLC.The process of chiral resolution of a-amino butylamide was carried out using L-(+)-tartaric as a resolution agent, which is an ordinary and cheap chemical material can be utilized recycled.The desired product with high HPLC、ee%was obtaining.