4-甲基-2-(3-甲酰基-4-羟基苯基)-5-噻唑甲酸乙酯的合成工艺改进

Synthesis of 4-Methyl-2-(3-formyl-4-hydroxyphenyl)-5-thiazole Formic Acid Ethyl Ester

以对羟基苯甲醛为原料,经氰化、硫代酰胺化、环合、甲酰化合成得非布索坦中间体4-甲基-2-(3-甲酰基-4-羟基苯基)-5-噻唑甲酸乙酯。对合成工艺进行了改进,总收率52.4%。合成方法简单易行,对仪器设备腐蚀性小,操作安全,节约成本,适于工业化生产。

4-Methyl-2-（3-formyl-4-hydroxyphenyl）-5-thiazole formic acid ethyl ester was synthesized by using p-hydroxybenzaldehyde as raw material through the following reactions including cyanide, thioamide, cyclization, and formylation reaction. A total yield of 52.4% was achieved due to improvement on the technology of febuxostat intermediate synthesis. In addition, the structures of the intermediates and target compound were confirmed by 1H NMR. The research results indicated that this synthesis method had the advantages including simple, less corrosive to equipment, high safety and low cost, and was suitable for industrial production.