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张秋月, 尤启冬, 杨金鹏. 托莫西汀合成工艺改进[J]. 中国药科大学学报, 2019, 50(4): 405-409. DOI: 10.11665/j.issn.1000-5048.20190404
引用本文: 张秋月, 尤启冬, 杨金鹏. 托莫西汀合成工艺改进[J]. 中国药科大学学报, 2019, 50(4): 405-409. DOI: 10.11665/j.issn.1000-5048.20190404
ZHANG Qiuyue, YOU Qidong, YANG Jinpeng. Process improvement on the synthesis of atomoxetine[J]. Journal of China Pharmaceutical University, 2019, 50(4): 405-409. DOI: 10.11665/j.issn.1000-5048.20190404
Citation: ZHANG Qiuyue, YOU Qidong, YANG Jinpeng. Process improvement on the synthesis of atomoxetine[J]. Journal of China Pharmaceutical University, 2019, 50(4): 405-409. DOI: 10.11665/j.issn.1000-5048.20190404

托莫西汀合成工艺改进

Process improvement on the synthesis of atomoxetine

  • 摘要: 托莫西汀是一种高度选择性去甲肾上腺素再摄取抑制剂。本文在文献方法的基础上,对托莫西汀的合成工艺进行了改进。以3-氯-1-苯基丙-1-酮为原料,经不对称还原、Mitsunobu反应、缩合反应3步得到光学纯的目标产物,总收率26%。本研究将第3步甲胺化的封管操作改为了常压下反应,增大了工业化可行性。改进后的工艺操作简化,反应条件温和,为托莫西汀的制备提供了一种新的方法。

     

    Abstract: Atomoxetine is a highly selective norepinephrine reuptake inhibitor. Based on the analysis of the literature methods, the synthesis process of atomoxetine was improved. Using 3-chloropropiophenone-1 as the raw material, optically pure target product was obtained by asymmetric reduction, Mitsunobu reaction and condensation reaction in three steps, with a total yield of 26%. The third-step methylation sealing operation was changed to the reaction under normal pressure, which increased the feasibility of industrialization. The improved process operation was simplified and the reaction conditions were mild, which would provide a new method for the preparation of atomoxetine.

     

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