去甲文拉法辛的合成

    Synthesis of Desmethylvenlafaxine

    • 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。

       

      Abstract: 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.

       

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