米拉贝隆中间体2-氨基噻唑-4-乙酸的合成

摘要

Amino thiazole-4-2-ethyl acetate(2) was obtained by cyclization reaction, using cyanamide, elemental sulfur and chlorine ethyl acetoacetate as the starting materials, and TsOH·H2O as the catalyst.The intermediate for Mirabegron, aminothiazole-4-2-acetic acid, was synthesized by hydrolysis reaction of 2.The structure was confirmed by 1H NMR, 13C NMR, IR and elemental analysis.The yield of 2 was 88.2% under the optimum reaction conditions[1 0.25 mol, TsOH·H2O 0.01 mol, reaction at 80 ℃, the recrystallization solvent was (EtOH/H2O=1/1, V/V)].%以氰胺、硫和氯乙酰乙酸乙酯为原料,一水合对甲苯磺酸(TsOH·H2O)为催化剂,经成环反应制得2-氨基噻唑-4-乙酸乙酯(2);2经水解反应合成了米拉贝隆中间体2-氨基噻唑-4-乙酸,其结构经1H NMR, 13C NMR, IR和元素分析确证.在最佳反应条件[1 0.25 mol, TsOH·H2O 0.01 mol,反应温度为80 ℃,重结晶溶剂(乙醇/水=1/1, V/V)]下,2收率88.2%.