Study On Synthesis Technology Of Levetiracetam

Levetiracetam is a novel antiepileptic drug, which has a unique antiepileptic mechanism, and the pharmacokinetic profile of levetiracetam closely approximates the ideal characteristics expected. In treatment of epilepsy, it’s not only used as adjuvant therapy, but also as monotherapy. Levetiracetam has broad market prospects.In this paper, three routes were discussed by using (S)-2-amino butyric acid as the started material, and two problems were discovered:(1) Strong base condition would lead to the racemization reaction.(2) Yield is unsatisfactory, as the yield of cyclization reaction is about50-60%according to the literature.Based on research and analysis of literature, the process route was optimized, with CH2C12as solvent. The reaction temperature was-5degree, material ratio was (S)-2-aminobutanamide hydrochloride:4-Chlorobutyryl chloride:KOH=1:1:2:3, material KOH and4-Chlorobutyryl chloride were added into three times using cross-feeding method. The yield of the reaction was considerably increased, the yield of cyclization reaction was about85%, and total yield reached64%. Further studies on solvent recycling and waste treatment provided data backing for industrial production.The route had the following advantages:material is universal and cheap, intermediate and production is stable, process is green. Overall, it’s a suitable technology for large production.