头孢吡肟中间体7-MPCA合成的研究

Study on Synthesis of Cefepime Intermeidiate 7-MPCA

以7-ACA为原料,经硅烷化、碘代、上环、脱保护基、成盐制得头孢吡肟中间体7-氨基-3-(1-甲基1--四氢吡咯)甲基-3-头孢-4-羧酸盐酸盐(7-MPCA)的盐酸盐,用核磁共振对样品结构进行了表征。研究了硅烷化试剂、溶剂、原料配比等因素对合成头孢吡肟中间体7-MPCA的影响,结果表明:二氯甲烷与环戊烷体积比1∶1是上环取代反应的较佳溶剂比例;7-ACA、三甲基氯硅烷、咪唑、N-甲基吡咯烷的较佳原料配比(物质的量比)为1∶2.8∶2.4∶1.5;硅烷化反应温度为45℃,时间2.5 h;上环取代反应的温度为-10℃,时间为2 h;产率可达96%。

7-amino-3-（1-methyl-1-pyrrolidino）methylceph-3-em-4-carboxylate hydrochloride is synthsized from 7-ACA by five steps：protected by silane,replaced by iodine,displacement,romove the protected group,form salt.The characteristics of the title compound is investigated with HNMR.The effect of some factors such as silane,solvent,and the ratio of raw material on the synthesis the title compound are studied.The result shows that the suitable volume ratio of methylene chloride and cyclopentane is 1∶1;the optimum ratio is 7-ACA∶chlorotrimethylsilane∶imidazole∶N-methyl pyrrole is 1∶2.8∶2.4∶1.5;the silane reactiong temperature is 45 ℃,the reaction time is 2.5 h;the reaction temperature of displacement is-10 ℃,the reaction time is 2 h;the overall yield can acheives 96%.