4-溴乙基-5-氟嘧啶的合成

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%。

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

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-(1Bromoethyl)-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%.