正交实验法优化阿伐他汀合成工艺  

Optimum synthesis process of atorvastatin by orthogonal experiment

作　　者：余丽丽[1] 杨宽[1] 姚琳[1] 白林奎 刘娅[1] 贺宇[1] 

机构地区：[1]西安医学院药学院,陕西西安710021

出　　处：《应用化工》2013年第11期1972-1974,共3页Applied Chemical Industry

基　　金：国家自然科学基金青年基金(81302706);陕西省教育厅科研计划项目(2013JK0759);西安医学院博士科研启动基金(2011DOC05);西安医学院校级科研计划大学生科研项目(12DXS01);陕西省大学生创新创业训练计划项目(201211840002)

摘　　要：以中间体M4和ATS-9为原料，通过Paal—Knorr缩合反应，合成含吡咯环的中间体，经过水解、脱保护，得到产物阿伐他汀。在单因素考察温度和甲苯加入量的影响的基础上，采用正交实验方法考察了反应温度、物料比、甲苯用量、反应时长等因素对产率的影响。结果表明，最佳反应条件为：温度为80℃，M4：ATS-9质量比为4：6，甲苯用量为3mL，反应时长为24h。在此条件下，产率为57％～61％。The atorvastatin intermediates, which was using to obtain atorvastatin by acid treatment and al- kali treatment,was prepared by Paal-Knorr method using M-4 and ATS-9 as raw materials. The synthesis conditions including temperature and the addition of toluene was researched. Then, the orthogonal design method was used to investigate the influence of the reaction temperature, the material ratio, the amount of toluene and the reaction time on the yield of atorvastatin. The results showed that the optimun reaction condition were as follows：the temperature is 80℃, M-4：ATS-9 is 4： 6, toluene dosage is 3 mL, and the reaction time is 24 h. Under the condition,the yield is about 57% - 61%.

关 键 词：阿伐他汀 合成 正交实验 

分 类 号：TQ463[化学工程—制药化工] R972.6[医药卫生—药品]