N-[2-(4-特戊酰氧基苯磺酰胺基)苯甲酰基]甘氨酸苄酯的合成

Synthesis of N-[2-(4-trimethylacetoxyb enzenesulphonamino) benzoyl]glycine benzyl ester

目的合成西维来司钠(sivelestatsodium)的关键中间体N-[2-(4-特戊酰氧基苯磺酰胺基)苯甲酰基]甘氨酸苄酯(1)。方法先以特戊酸、氯化亚砜、对羟基苯磺酸为原料,经酯化、苯磺酸成酰氯得到对位特戊酰氧基苯磺酰氯(4);再以甘氨酸、苄醇、邻硝基苯甲酰氯为原料经酯化、酰氨化、还原得到N-(2-氨基苯甲酰基)甘氨酸苄酯(7);将4和7两中间体缩合得1。结果及结论本方法原料廉价易得,条件温和易控,收率较高,适合工业化生产。

Aim To synthesize the key intermediate of sivelestat sodium, N-[2-（4-trimethylacetoxybenzenesulphonamino）benzoyl]glycine benzyl ester. Method Trimethylacetic acid, thionyl chioride and p-hydroxybenzenesulfonic acid was treated by esterification, sulfonyl chloride formation to give trimethylacetoxybenzenesulfonic chloride （4）. Glycine, benzyl alcohol and o-nitrobenzoyl chloride was treated by esterification, acylamination and reduction to give N- （2-aminobenzoyl） glycine benzyl alcohol ester （7）. The target compound was obtained by condensation between （4） and （7）. Results and conclusion The raw materials in this route is cheap, and the reaction condition is easy to control. Yield is higher and this method can be applied in industry production.