奥拉西坦的合成工艺改进

Improvement of Synthesis Technics of Oxiracetam

奥拉西坦为吡咯烷酮类衍生物,用于脑损伤及引起的神经功能缺失、记忆与智能障碍的治疗。针对奥拉西坦合成工艺存在合成路线长、废固较多、操作复杂、产品不易提纯等问题,提出了一种合成奥拉西坦的改进方法,即以4-氯乙酰乙酸乙酯和甘氨酰胺为原料合成奥拉西坦,研究了催化剂、反应溶剂、反应时间对反应体系的影响,找到了最佳优化条件：环合反应p H值为10.5~11.0,乙醇水溶液比例为1∶8,甘氨酰胺配比为1∶1.0,环合反应溶剂配比为1∶25,环合反应温度为77~78℃,催化剂用量为1∶100,反应时间为12~14 h。该方法具有原料易得,制备过程简单、产率较高,适宜工业生产等优点。

Oxiracetam is a kind of pyrrolidone derivatives that used for the treatment of brain damage and neurological deficit, impediment of anamnesis and aptitude that caused by brain damage. Aiming at the problems that exist in the synthesis technics of oxiracetam which are too many steps in the synthesis process, too much solid waste, complex operation, and products difficult to purification etc., a new improved method for the synthesis of oxiracetam is proposed,that is ethyl 4- chloroacetoacetate and glycinamide as the raw materials to synthesize oxiracetam. The influences of catalyst,reaction solvent, reaction time on the reaction system were studied. The found best optimum conditions are cyclization reaction p H is 10.5~11.0, the proportion of ethanol water is 1∶8, ratio of glycinamide is 1∶1.0, ratio of the cyclization reaction solvent is 1∶25, cyclization reaction temperature is 77~78℃, the amount of catalyst is 1∶100, and the reaction time is 12 ~ 14 h. The method has the advantages such as raw materials are easy to get, the manufacturing process is simple, high yield, suitable for industrial production and so on.