CAJ | 학술논문

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.
이(S)-2-안기정선알위수성원합성좌을랍서탄적로선주요유량조:일시화4-추정산을지반응,경친핵취대재배합득목표화합물;이시화4-록정선록반응,재감성조건화상전이최화제작용하,경선알화재배합득목표화합물.로선일재반응과정중유쌍을선화잡질산생,난이제거,조성유관물질편고,차정개반응시간교장;로선이재이PEG-400위상전이최화제조건하,반응시간대대축단,차무상술적쌍을선화잡질.로선이조작간단역행,경역공업화.
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.