Hydroxyl groups in (4S)-3-[(5S)-5-(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one (Ⅱ) and 4-{[(4-fluorophenyl)imino]methyl}phenol (Ⅲ) were protected by chlorotrimethylsilane and N,O-bis(trimethylsilyl)acetamide, respectively. Then key intermediate of ezetimibe, (S)-3-{(2R,5S)-5-(4-fluorophenyl)-2-((S)-[(4-fluorophenyl)amino]{4-[(trimethylsilyl)oxy]phenyl}methyl)-5-[(trimethylsilyl)oxy]pentanoyl}-4-phenyloxazolidin-2-one (Ⅰ) was obtained by Mannich-like reaction with TiCl4 as catalyst and dichloromethane as solvent. The structure of product was characterized by 1HNMR, 13CNMR, MS, FTIR and polarimeter. The effects of molar ratio of reactants and reaction temperature on the yield of product Ⅰ were investigated by single factor method. The optimum conditions were obtained as follows：n(Ⅱ)∶n(Ⅲ)∶n(TiCl4)=1.0∶1.5∶1.2, reaction time of 4.0 h, reaction temperature between -30 and -25 ℃. Under the above conditions, product Ⅰ had a yield of 63.17% and purity of 97.28%. The purity of Ⅰ could be improved to 98.96% after the refining.