4-溴乙基-5-氟嘧啶的合成  

Synthesis of 4-(1-bromoethyl)-5-fiuoropyrimidine

作　　者：赵敏[1] 王德才[1] 

机构地区：[1]南京工业大学制药与生命科学学院,江苏南京210009

出　　处：《化工时刊》2007年第7期16-18,共3页Chemical Industry Times

摘　　要：伏立康唑是由美国辉瑞公司研究开发的第二代三唑类抗真菌药物,具有抗菌谱广,抗菌效力强的特点。4-溴乙基-5-氟嘧啶是合成伏立康唑的重要中间体,在对文献中几条工艺路线分析比较的基础上,优化出一条较为理想的合成工艺路线,该路线以5-氟尿嘧啶为起始原料,经三氯氧磷氯化,与溴化乙基镁通过格氏反应乙基化,经高锰酸钾氧化后进行氢解脱氯,再经N-溴代琥珀酰亚胺溴化制得4-溴乙基-5-氟嘧啶。总收率为45.8%。Voriconazole is a second generation triazole antifungal agent that shows the characters of broad - spectrum and strong antibacterialaction. 4- （1 - Bromoethyl） - 5 - fluoropyrimidine is an important intermediate of preparation for voriconazole. The purpose of thesis is to study the synthetic routes of 4 - （ 1 - bromoethyl） - 5 - fluoropyrimidine. Several methods about synthesis of 4 - （ 1 - bromoethyl） - 5 - fiuoropyrimidine were reported. The selection and development of the reasonable and feasible synthetic route of 4 - （ 1 - bromoethyl） - 5 - fluoropyrimidine were introduced. 4 - （ 1 - Bro- moethyl） -5 -fluoropyrimidine was synthesized from 5 -fiuorouracil by chlorization with phosphorus oxychloride, Grignard reaction with ethylmagnesium bromide, oxidation with potassium permanganate, hydrogenolysis with hydrogen, and bromization with N - bromosuccinimide. The total yield was 45.8 %.

关 键 词：伏立康唑 4-溴乙基-5-氟嘧啶 中间体 5-氟嘧啶 合成 

分 类 号：TQ463.53[化学工程—制药化工]