左乙拉西坦的合成

SYNTHESIS OF LEVETIRACETAM

目的合成左乙拉西坦并且优化合成工艺。方法以(S)-2-氨基丁酸为原料,经酯化、氨解得中间体(S)-2-氨基丁酰胺盐酸盐,再与4-氯丁酰氯进行酰化反应,经分子内亲核取代反应,环合后得目标化合物左乙拉西坦。结果经元素分析、质谱、核磁共振氢谱确证目标化合物的化学结构,经高效液相色谱法测定,其纯度达99.75%,总收率为46.6%。结论本方法制备左乙拉西坦,操作简便,收率较高,适用于工业化生产。

Objective To synthesize levetiracetam and to improve the synthesis process. Methods Levetiracetam, as a new antiepileptic drug, was synthesized from （S）-2-aminobutyric acid via esterification and aminolysis to give （S）-2-aminobutyramide hydrochloride, which was subjected to condensation with 4-chloride butyryl chloride, and then cyclized intramolecularly. Results The total yield of levetiracetam was 46.6 % ,the purity was 99.75% （high performance liquid chromatography）, and its structure was confirmed by elemental analysis （EA）, mass spectrum （MS）and 1H NMR spectroscopy. Conclusion The synthetic route for levetiracetam was convenient for industrial manufacture with simple operation and high yield.