苯基吡拉西坦的合成工艺研究

Synthesis of 4-Phenyl-2-pyrrolidone-1-acetamide

苯基吡拉西坦是一类新型促智药。以4-氨基-3-苯基丁酸盐酸盐为原料与甲醇发生酯化反应、然后在三乙胺作用下发生氨解环合反应,合成中间体4-苯基-2-吡咯烷酮(1)。在氢化钠存在下,4-苯基-2-吡咯烷酮与溴乙酸乙酯发生烷基化反应,生成2-氧代-4-苯基-1-吡咯烷乙酸乙酯(2)。然后在室温下与氨水再次经氨解得到目标产物苯基吡拉西坦(3)。将4-苯基-2-吡咯烷酮的合成路线缩短为一步反应。总体反应路线步骤短,条件温和,对设备要求不苛刻,适合工业化生产。目标产物及中间体经1 H NMR和IR表征。

4-Phenyl-2-pyrrolidone-1-acetamide is a new type of nootropic drugs.An intermediate of 4-phenyl-2-pyrrolidone was synthesized from 4-amino-3-phenyl butyric acid hydrochloride by esterification and ammonolysis reactions with methanol and triethylamine,respectively.Alkylation of 4-phenyl-2-pyrrolidone(1)with ethyl bromide was carried out in the presence of sodium hydrogen so that 2-oxo-4-phenyl-1-pyrrolidineacetic acid ethyl ester(2)was produced.The target product(3)was obtained through the ammonolysis reaction using ammonia at room temperature.The synthetic route of compound 1 in literature is shortened to a one-step reaction.The overall reaction route is short,the conditions are mild,the equipment requirements are not harsh and is suitable for industrial production.The product and intermediates were confirmed by^1H NMR and IR.