5-氟尿嘧啶合成工艺研究

以氟乙酸甲酯为原料，在甲醇钠催化下与甲酸乙酯缩合得氟代甲酰乙酸酯烯醇式钠盐（化合物Ⅱ），化合物Ⅱ与O-甲基异脲硫酸盐环合得2-甲氧基-5-氟尿嘧啶（化合物V），V在稀盐酸中水解为5-氟尿嘧啶。在n（氟乙酸甲酯）：n（钠）：n（甲酸乙酯）：n（O-甲基异脲硫酸盐）；1．0：3．0：2．5：1．0、缩合温度为35℃、缩合时间为2h、环合温度为40℃、环合时间为6h以及水解温度为60℃的最佳反应条件下，目标化合物总收率为45．3％、纯度大于95％，其结构经IR、1^HNMR确证。

Study on Synthetic Technique of 5-Fluorouracil

Condensing methyl fluoroacetate and ethyl formate in the presence of sodium methoxide with the formation of alkylformylfluoroacetate enolate,which was not separated and reacted immediately with O-methyl- isourea hemisulfate to form the intermediate of 2-methoxyl-5-fluorouracil, followed by hydrolysis in aqueous chlorie acid to obtain 5-ftuorouraeil. The yield of 5-fluorouracil was 45.3 % and its purity was above 95 % under the optimum conditons as follows：molar ratio of methyl fluoroacetate to sodium methoxide to ethyl formate to O-methylisourea hemisulfate was 1.0 ： 3.0 ： 2.5 ： 1.0,condensation temperature was 35 ℃ ,condensation time was 2 h,eyclization temperature was 40 ℃ ,cyclization time was 6 h,and hydrolysis temperature was 60 ℃. The object product had been characterized bY IR and 1^HNMR.