消旋托莫西汀的合成研究-河北科技大学学报.PDF

29 4 Vol. 29, No .4 2008 12 Journal of Hebei University of Science and T ec nology Dec. 2008 : 1008-1542( 2008) 04-0328- 04 1 1 2 2 李爱军, 靳淑委 , 段 颖 , 张亚通 ( 1. 河北科技大学化学与制药工程学院, 河北石家庄 050018; 2. 河北科技大学理学院, 河北石家庄 050018) : 对盐酸托莫西汀的关键中间体消 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 托莫西汀, 总收率为68. 1% , 纯度为99. 5% : 托莫西汀; 抗抑郁药; 合成 : R914 : A Study on synt esis of atomoxetine ydroc loride 1 1 2 2 LI Ai-jun , JIN S u-w ei , DUAN Ying , ZHAN G Ya-tong ( 1. College of C emical and P armaceutical Engineering, H ebei Universit y of Science and Tec nology , S ijiaz uang H ebei 050018, C ina; 2. College of Sciences, H ebei Universit y of Science and Tec nology, S ijiaz uang Hebei 050018, C ina) Abstract : In t is paper, w e did a researc on optimization for synt esis of racemic atomoxet ine w ic is a very important inter- mediate for t e synt esis of atomoxetine ydroc loride. It w as synt esized using 3- met ylamino-1-p enylpropanol as t e start- ing material via suc t ree steps as et erification, purificat ion and salt formation. Opt imum reaction condit ions w ere obtained w ile t e effects of raw materials molar ratio, reaction temperature and p ase t ransfer catalyst on t e reaction were studied in et erification, and t e influence of purificat ion met ods and salt formation was investigated. At omoxetine ydroc loride w as pre- pared by reaction of 3-met ylamino- 1-p enylpropanol wit 1-fluoro-2-met ylbenzene in DMSO/ KOH and salt formation, w it t e total yield of 68. 1% , and puri