Synthesis of Two Impurities in Cholesterol Absorption Inhibitor Ezetimibe

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.