司氟沙星合成新工艺研究

Study on new process of synthesizing sparfloxacin

目的:合成氟喹诺酮类抗菌药司氟沙星。方法:以2,3,4,5-四氟苯甲酸为原料,经硝化、酰氯化后与N,N-二甲氨基丙烯酸乙酯偶联,再经环丙胺取代、催化环合、硝基还原、酸性水解等反应,最后与顺式-2,6-二甲基哌嗪缩合。结果与结论:该法缩短了工艺流程,反应条件温和,三废减少,收率有所提高(总收率为34.2%),有较好的工业应用前景。

Objective： To study a new process for preparing the fluoroquinolone antibacterial drug sparfloxacin. Methods： The objective compound was prepared from 2,3,4,5-tetrafluorobenzoic acid, via nitration and acyl chlorination before coupling with ethyl N,N-dimethylamino- acrylate, cyclopropylamine displacement, cyclization, reduction, hydrolysis, and then condensation with 2,6-dimethylpiperazine. Result and Conclusion： The total yield was 34.2% of the input. Different from the old process, the new one can curtail three reaction steps;diethyl malonate condensation, partial hydrolysis decarboxylation, and triethylorthoformate condensation. The new process has many advantages, including short reaction period, mild reaction condition, waste reduction, yield increase, with a good prospect for industrial application.