5-氟-6-乙基-4-羟基嘧啶的合成

Synthesis of 5-fluoro-6-ethyl-4- hydroxy-pyrimidine

摘要:

以α-氟代丙酰乙酸乙酯为原料，用氨化和环合的“一锅法”反应合成了伏立康唑的关键中间体——5-氟-6-乙基-4-羟基嘧啶；最优的反应条件为：以甲醇钠作为碱，氨气作为氨化试剂，甲醇作为反应的溶剂，先在室温下搅拌反应5h，然后加入甲酰胺后回流搅拌反应5h，两步总收率63%。

Abstract:

The key intermediate of voriconazole, 5-fluoro-6-ethyl-4-hydroxy-pyrimidine was synthesized by a "One pot" ammoniated and cyclization reaction with α-fluoro-ethyl propionyl as raw material. The optimal reaction conditions is: sodium methoxid, ammonia stirred in methanol at room temperature for 5 hours, then added carboxamide; stirred under reflux for another 5 hours; the over all yield of is 63%.