消旋托莫西汀的合成研究

Study on synthesis of atomoxetine hydrochloride

对盐酸托莫西汀的关键中间体消旋托莫西汀的合成工艺进行了优化研究,设计了一条以3-甲氨基-1-苯基丙醇为原料,经过醚化反应、提纯、成盐的合成路线。在醚化反应中考察了原料物质的量比、反应温度、相转移催化剂对反应的影响,研究了提纯方式及成盐的影响,得到了最佳的反应条件。用3-甲氨基-1-苯基丙醇与邻氟甲苯在DMSO/KOH体系中进行醚化反应,成盐制得消旋托莫西汀,总收率为68.1%,纯度为99.5%。

In this paper, we did a research on optimization for synthesis of racemic atomoxetine which is a very important intermediate for the synthesis of atomoxetine hydroehloride. It was synthesized using 3-methylamino-1-phenylpropanol as the starting material via such three steps as etherification, purification and salt formation. Optimum reaction conditions were obtained while the effects of raw materials molar ratio, reaction temperature and phase transfer catalyst on the reaction were studied in etherification,and the influence of purification methods and salt formation was investigated. Atomoxetine hydroehloride was prepared by reaction of 3-methylamino-1-phenylpropanol with 1-fluoro-2-methylbenzene in DMSO/KOH and salt formation, with the total yield of 68.1%, and purity of 99.5 %.