4-甲氧基乙酰乙酸甲酯的合成研究

摘要

4-Methoxyacetoacetic acid methyl ester was an important intermediate of dolutegravir. It was prepared in a total yield of 93%from 4-chloroacetoacetic acid methyl ester via substitution reaction with methanol in the presence of NaH and CH3 OK to give organic salts,followed by acidification and decoloration. The structures of these compounds were confirmed by 1H NMR and 13C NMR. This method could reduce by-product effectively.%4-甲氧基乙酰乙酸甲酯是合成抗HIV/AIDS新药度鲁特韦的重要中间体。以4-氯乙酰乙酸甲酯为原料，在氢化钠和甲醇钾的作用下发生取代反应，得到纯净的有机盐，然后在有机溶剂中加酸酸化、活性炭脱色，得到纯品4-甲氧基乙酰乙酸甲酯，总收率达到93%。产品经过核磁氢谱和核磁碳谱表征。该路线能有效减少副产物。