普芦卡必利关键中间体4-氨基-5-氯-2,3-二氢-7-苯并呋喃苯甲酸的合成工艺研究

Synthesis of 4- Amino- 5- Chloro- 2,3- Dihydrobenzofuran- 7- Carboxylic Acid,a Prucalopride's Synthetic Intermediate

目的研究普芦卡必利关键中间体4-氨基-5-氯-2,3-二氢-7-苯并呋喃苯甲酸的合成工艺。方法以2-甲氧基-4-乙酰氨基-5-氯苯甲酸甲酯为起始原料,经脱甲基、溴化、缩合、环合、水解得到目标产物。结果经五步合成了目标产物,总收率为63%,目标化合物结构经1HNMR和MS确证。结论该合成方法原料易得,反应条件温和,适合大规模制备。

Objective To study the synthetic process of 4- Amino- 5- chloro- 2,3- dihydrobenzofuran- 7- carboxylic acid,the key intermediate for the preparation of prucalopride.M ethods The target compound was prepared through demethylation,bromination,condensation,cyclization and hydrolysis reaction with 2- methoxy- 4- acetylamino- 5- chloro methyl benzoate as starting material.Results The target compound was obtained through a 5- step procedure in an overall yield of 63%.The structure of target compound was confirmed by ~1HNMR and MS.Conclusion The easy availability of the reactants,facile reaction conditions and convenient operation procedures make the process a promising prospect for application in large- scale manufacture.