| 不对称氢化、氢转移反应制备(R)-邻氯扁桃酸甲酯：(S)-氯吡格雷关键中间体的不对称合成 |
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| 引用本文： | 尹 璐,贾 娴,黎星术.不对称氢化、氢转移反应制备(R)-邻氯扁桃酸甲酯：(S)-氯吡格雷关键中间体的不对称合成[J].中国药物化学杂志,2009,19(6):416-419. |
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| 作者姓名： | 尹 璐 贾 娴 黎星术 |
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| 作者单位： | （1. 沈阳药科大学 制药工程学院，辽宁 沈阳 110016； ;2. 中山大学 药学院，广东 广州 510080） |
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| 摘 要： | 目的 用不对称氢化、氢转移方法制备合成(S)-氯吡格雷的关键中间体——(R)-邻氯扁桃酸甲酯。方法 以α-邻氯扁桃酮酸甲酯为起始原料，分别用不对称氢化和氢转移方法制备(R)-邻氯扁桃酸甲酯。结果与结论 使用不对称氢化方法制备(R)-邻氯扁桃酸甲酯，对映选择性为64.8% ,用氢转移方法，优化催化条件后目标产物的ee值高达92.6%，从而为(S)-氯吡格雷的不对称合成奠定了基础。
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| 关 键 词： | 不对称氢化反应 氢转移反应 (R)-邻氯扁桃酸甲酯 (S)-氯吡格雷 |
| 收稿时间： | 2009-8-19 |
| 修稿时间： | 2009-10-10 |
Preparation of methyl (R)-o-chloromandelate by asymmetric hydrogenation and transfer hydrogenation: enantioselective synthesis of the key intermediate for (S)-clopidogrel |
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| YIN Lu,JIA Xian,LI Xing-shu.Preparation of methyl (R)-o-chloromandelate by asymmetric hydrogenation and transfer hydrogenation: enantioselective synthesis of the key intermediate for (S)-clopidogrel[J].Chinese Journal of Medicinal Chemistry,2009,19(6):416-419. |
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| Authors: | YIN Lu JIA Xian LI Xing-shu |
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| Institution: | (1. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China; 2. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China) |
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| Abstract: | Aim To prepare methyl (R)-o-chloromandelate (key intermediate for (S)-clopidogrel) by asymmetric hydrogenation and transfer hydrogenation. Methods methyl (R)-o-chloromandelate was prepared by asymmetric hydrogenation and asymmetric transfer hydrogenation from methyl o-chlorobenzoylformate. Results and conclusion 64.8% ee was achieved for methyl (R)-o-chloromandelate by asymmetric hydrogenation, while enantioselectivity was up to 92.6% ee for the key intermediate for (S)-clopidogrel under an optimal condition by asymmetric transfer hydrogenation. |
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| Keywords: | asymmetric hydrogenation transfer hydrogenation methyl (R)-o-chloromandelate (S)-clopidogrel |
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