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本研究报道了一条合成枸橼酸莫沙必利(1)的新路线。以对氨基水杨酸钠(2)为起始原料,经乙酰化、双乙基化和氯化得2-乙氧基-4-乙酰胺基-5-氯苯甲酸乙酯(5)。化合物5不经水解直接与2-氨甲基-4-(4-氟苄基)吗啉缩合得2-乙氧基-4-乙酰胺基-5-氯-N-[[4-(4-氟苄基)-2-吗啉基]甲基]苯甲酰胺(6),6在枸橼酸作用下脱保护并成盐得1,纯度99.92%,总收率58.9%(以2计)。该法反应条件温和,操作简便,成本较低,终产品纯度高,符合国际标准。本路线中由关键中间体5制备1的方法未见文献报道。
This study reports a new route for the synthesis of mosapride citrate (1). Using sodium p-aminosalicylate (2) as the starting material, ethyl 2-ethoxy-4-acetamido-5-chlorobenzoate (5) was obtained by acetylation, bisethylation and chlorination. Compound 5 was directly condensed with 2-aminomethyl-4- (4-fluorobenzyl) morpholine without hydrolysis to give 2-ethoxy-4-acetamido-5-chloro-N - [[4- -fluorobenzyl) -2-morpholinyl] methyl] benzamide (6), 6 was deprotected and salified by citric acid to give a purity of 99.92% and a total yield of 58.9% (calculated as 2 ). The reaction conditions mild, easy to operate, lower cost, high purity of the final product, in line with international standards. The preparation of 1 from the key intermediate 5 in this route has not been reported in the literature.