以(S)-2-氨基丁酰胺盐酸盐为手性源合成左乙拉西坦的工艺比较

以(S)-2-氨基丁酰胺为手性源合成左乙拉西坦的路线主要有两条:一是和4-溴丁酸乙酯反应,经亲核取代再环合得目标化合物;二是和4-氯丁酰氯反应,在碱性条件和相转移催化剂作用下,经酰胺化再环合得目标化合物.路线一在反应过程中有双乙酰化杂质产生,难以除去,造成有关物质偏高,且整个反应时间较长;路线二在以PEG-400为相转移催化剂条件下,反应时间大大缩短,且无上述的双乙酰化杂质.路线二操作简单易行,更易工业化.

Comparison on synthesis process of levetiracetam starting by use of(S)-2-amino-butanamide hydrochloride as a chiral resource

At present,there are two routes to synthesize levetiracetam by use of(S)-2-aminobutanamide hydrochloride as a chiral resource.In the first route,the target compound is synthesized by reaction of(S)-2-aminobutanamide hydrochloride with ethyl 4-bromobutyrate via nucleophilic reaction and cyclization.In the second way,the target compound is also obtained by reaction of(S)-2-aminobutanamide hydrochloride with 4-chlorobutyryl chloride via amidation and cyclization in the presence of base and phase transfer catalyst.The results showed that diacetylation impurity amount was high and therefore reaction time was too long for the first route,the most reason is that diacetylation impurity is difficult to be removed.Comparably,for the second route,there was no diacetylation impurity and therefore reaction time was shorter than that for the first route,the most reason is that PEG-400 is used as a phase transfer catalyst,so,this method is simple and easy for industrial application.