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右旋雷贝拉唑钠的制备工艺改进

张春来, 罗宏军, 姜琦, 李国贤, 顾国庆, 张杰

张春来, 罗宏军, 姜琦, 李国贤, 顾国庆, 张杰. 右旋雷贝拉唑钠的制备工艺改进[J]. 中国药科大学学报, 2018, 49(3): 291-294. DOI: 10.11665/j.issn.1000-5048.20180306
引用本文: 张春来, 罗宏军, 姜琦, 李国贤, 顾国庆, 张杰. 右旋雷贝拉唑钠的制备工艺改进[J]. 中国药科大学学报, 2018, 49(3): 291-294. DOI: 10.11665/j.issn.1000-5048.20180306
ZHANG Chunlai, LUO Hongjun, JIANG Qi, LI Guoxian, GU Guoqing, ZHANG Jie. Improved process of dexrabeprazole sodium[J]. Journal of China Pharmaceutical University, 2018, 49(3): 291-294. DOI: 10.11665/j.issn.1000-5048.20180306
Citation: ZHANG Chunlai, LUO Hongjun, JIANG Qi, LI Guoxian, GU Guoqing, ZHANG Jie. Improved process of dexrabeprazole sodium[J]. Journal of China Pharmaceutical University, 2018, 49(3): 291-294. DOI: 10.11665/j.issn.1000-5048.20180306

右旋雷贝拉唑钠的制备工艺改进

Improved process of dexrabeprazole sodium

  • 摘要: 为改进右旋雷贝拉唑钠的制备工艺,简化合成步骤,提高产品质量和收率,获得稳定可行的生产工艺,以2-[[[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基]硫代]-1H-苯并咪唑为起始原料,以钛酸四异丙酯和L-酒石酸二乙酯为手性催化剂,以过氧化氢异丙苯为氧化剂对其进行不对称氧化得到右旋雷贝拉唑,精制后与氢氧化钠成盐得目标化合物,收率为79%,产品HPLC纯度99.6%以上。目标化合物经NMR、IR、元素分析、LC-MS确证其结构。改进后的工艺生产周期短,操作步骤简单,产品收率和纯度得到提高,适合工业化生产。
    Abstract: The aim of the work is to improve the synthetic process of dexrabeprazole sodium, enhance quality and yield of the product, simplify synthetic steps, and offer a stable and feasible process. Starting from 2-[[[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl] thio]-1H-benzimidazole, dexrabeprazole was produced by asymmetric oxidation reaction with oxidant cumene hydroperoxide in the presence of chiral catalyst tetraisopropyl titanate and L-(+)-tartaric acid diethyl ester. Dexrabeprazole sodium was obtained by the reaction of purified dexrabeprazole with sodium hydroxide in a total yield of 79% with an HPLC purity of > 99. 5%. The structure of dexrabeprazole sodium was confirmed by NMR, IR, elemental analysis and LC-MS. The improved process of dexrabeprazole sodium possesses simple operations, good yield and high purity, which is feasible for industrialization.
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出版历程
  • 刊出日期:  2018-06-24

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