去甲文拉法辛的合成  

Synthesis of Desmethylvenlafaxine

作　　者：薛娜[1] 张恺[2] 郝晓飞[2] 郝六平[1] 王乐[1] 

机构地区：[1]河北化工医药职业技术学院,石家庄050026 [2]河北医科大学药学院,石家庄050017

出　　处：《中国现代应用药学》2014年第2期151-154,共4页Chinese Journal of Modern Applied Pharmacy

基　　金：河北省自然科学基金资助项目(H2012206125);河北省科技计划项目(13272611);河北省教育厅青年基金项目(Q2012028);河北省科技支撑计划自筹经费项目(13272614)

摘　　要：目的合成去甲文拉法辛。方法以对羟基苯乙酸为原料,经羟基保护,水解得对苄氧基苯乙酸(3),再经二氯亚砜氯代,二甲胺胺解得N,N-二甲基-4-苄氧基苯乙酰胺(5),5在正丁基锂催化下与环己酮反应得N,N-二甲基-2-(1-羟基环己基)-4-苄氧基苯乙酰胺(6),6经BH3/THF还原,Pd/C催化氢解后制得目标化合物去甲文拉法辛(1)。结果目标化合物经元素分析、氢谱、质谱和红外光谱确证其化学结构,总收率为28.8%。结论本方法原料易得,收率高,产品纯度好,适合工业化生产。OBJECTIVE To synthesize O-desmethylvenlafaxine. METHODS Desmethylvenlafaxine was synthesized from p-hydroxylphenylacetic acid via etherification, chlorination and amination to give N, N-dimethyl-4-benzyloxy phenylacetamide （5）, which was subjected to condensation with cyclohexanone in the presence of n-BuLi to give 1-[（4-benzyloxyphenyl）-dimethylaminocarbonylmethyl] cyclohexanol （6）, and then followed by reduction using BH3/THF and hydrogenolysis with Pd/C to give desmethylvenlafaxine （1）. RESULTS The total yield of O-desmethylvenlafaxine was 28.8%, and its structure was confirmed by EA, ~H-NMR, MS and IR. CONCLUSION The synthetic route for O-desmethylvenlafaxine is convenient for industrial manufacture with high yield and good purity.

关 键 词：去甲文拉法辛 抗抑郁药 合成 

分 类 号：R914.5[医药卫生—药物化学]