| 引用本文: | 薛娜,张恺,郝晓飞,郝六平,王乐.去甲文拉法辛的合成[J].中国现代应用药学,2014,31(2):151-154. |
| XUE Na,ZHANG Kai,HAO Xiaofei,HAO Liuping,WANG Le.Synthesis of Desmethylvenlafaxine[J].Chin J Mod Appl Pharm(中国现代应用药学),2014,31(2):151-154. |
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| 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。 |
| 关键词: 去甲文拉法辛 抗抑郁药 合成 |
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| 基金项目: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) |
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| Synthesis of Desmethylvenlafaxine |
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XUE Na1, ZHANG Kai2, HAO Xiaofei2, HAO Liuping1, WANG Le1
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1.Hebei Chemical and Pharmaceutical College, Shijiazhuang 050026, China;2.School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China
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| 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. |
| Key words: O-desmethylvenlafaxine anti-depressant drug synthesis |
