| 引用本文: | 岳磊,王龙兴,段成军,马静洁.胆固醇吸收抑制剂依折麦布中2种杂质的合成[J].中国现代应用药学,2015,32(4):437-439. |
| YUE Lei,WANG Longxing,DUAN Chengjun,MA Jingjie.Synthesis of Two Impurities in Cholesterol Absorption Inhibitor Ezetimibe[J].Chin J Mod Appl Pharm(中国现代应用药学),2015,32(4):437-439. |
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| 摘要: |
| 目的 合成依折麦布原料药中的2种主要杂质。方法 依折麦布(1)经氯代铬酸吡啶盐(PCC)氧化制得杂质Ⅰ；以依折麦布中间体1-(4-氟苯基)-3(R)-[3-(4-氟苯基)-羟丙基]-4(S)-[4-(4-苄氧基)-苯基]-氮杂环丁烷-2-酮(2)为原料经催化氢化反应制得杂质Ⅱ。结果 所得2种杂质结构经1H-NMR、13C-NMR和ESI-MS确证，纯度经HPLC检测可达98%以上。结论 解决了依折麦布杂质的来源问题，为依折麦布的质量控制提供了依据。 |
| 关键词: 依折麦布 杂质 合成 |
| DOI： |
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| 基金项目:吉林省科技发展计划项目(20140309008YY) |
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| Synthesis of Two Impurities in Cholesterol Absorption Inhibitor Ezetimibe |
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YUE Lei1, WANG Longxing2, DUAN Chengjun2, MA Jingjie1
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1.Yanbian University, Yanji 133000, China;2.Broadwell Pharmaceutical Co., Ltd., Changchun 130000, China
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| Abstract: |
| OBJECTIVE To synthesize two impurities(Ⅰ and Ⅱ) in ezetimibe. METHODS Impurty Ⅰwas obtained from ezetimibe(1) by oxidation using pyridinium chlorochromate(PCC), impurty Ⅱ was gained from intermediate 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-hydroxypropyl]-4(S)-[4-(4-benzyloxy)-phenyl]-azetidine-2-one(2) of ezetimibe by catalytic hydrogenation. RESULTS The structures of two impurities were verified by 1H-NMR, 13C-NMR and ESI-MS. The purities were over 98% as determined by HPLC. CONCLUSION It solves the problem of impurities source and provides a basis for quality control of ezetimibe. |
| Key words: ezetimibe impurity synthesis |
