去甲文拉法辛的合成

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MM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。

Synthesis of Desmethylvenlafaxine

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, 1H-NMR, MS and IR. CONCLUSION The synthetic route for O-desmethylvenlafaxine is convenient for industrial manufacture with high yield and good purity.