卡非多的合成工艺研究

目标化合物是一种可以促进认知能力,增强记忆力的中枢神经系统用药。以苯乙腈为原料与氯乙酸乙酯发生取代反应生成3-腈基-3-苯丙酸乙酯,然后在催化剂作用下发生还原反应及自身缩合,合成4-苯基-2-吡咯烷酮。在氢化钠存在下,4-苯基-2-吡咯烷酮与溴乙酸乙酯反应,生成2-氧代-4-苯基-1-吡咯烷乙酸乙酯。然后在室温下与氨水经氨解得到目标化合物。总体反应路线较其他路线成本低、反应简单、副产物少、适合工业化生产。优化后反应的总收率为71.49%,目标化合物及中间体经1HNMR表征。

Synthesis of Carphedon

The target compound is a central nervous system drug that can promote cognitive ability and enhance memory.Ethyl 3-nitrile-3-phenylpropionate was synthesized from phenylacetonitrile by substitution reaction with ethyl chloroacetate.Then,4-phenyl-2-pyrrolidone was synthesized by reduction reaction and self-condensation with catalyst.In the presence of sodium hydride,4-phenyl-2-pyrrolidone reacted with ethyl bromoacetate to form 2-oxo-4-phenyl-1-pyrrolidine ethyl acetate.Then the target product was obtained by ammonia hydrolysis with ammonia water at room temperature.Compared with other routes,the overall reaction route has the advantages of low cost,simple reaction and less by-products,which is suitable for industrial production.The total yield of the optimized reaction was 71.49%.The target products and intermediates were confirmed by 1HNMR.