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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。
Objective To synthesize two major impurities in ezetimibe drug substance. The method was based on the oxidation of ethylzinc (1) with pyridinium chlorochromate (PCC) to obtain the impurity I. The ezetimibe was prepared by the reaction of ezetimibe with 1- (4-fluorophenyl) -3 (R) 4-Fluorophenyl) -hydroxypropyl] -4 (S) - [4- (4-benzyloxy) -phenyl] -azetidine-2-one (2) Obtained impurities Ⅱ. Results The two impurity structures were confirmed by 1H-NMR, 13C-NMR and ESI-MS. The purity of the two impurities was over 98% by HPLC. Conclusion The problem of the origin of ezetimibe was solved, which provided the basis for the quality control of ezetimibe.