(4S)-3-[5-(4-Fluorophenyl)-1,5-dioxopenyl]-4-phenyl-2-oxazolidinone

99395-88-7

149437-76-3

189028-93-1

Example 1: Preparation of ezetimibe; (1-1) Preparation of (4S)-3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone (Eq. 7); A reaction mixture was prepared by dissolving 200 g of 5-(4-fluorophenyl)-5-oxopentanoic acid (Eq. 8), 160 g of (S)-4-phenyl-oxazolidin-2-one (Eq. 9), and 11.6 g of 4- dimethylamino pyridine were dissolved in 600 mL of dichloromethane to prepare the reaction mixture. A solution prepared by dissolving 157 g of N,N'-dicyclohexylcarbimide in 200 mL of dichloromethane was added to the reaction mixture and stirred for 2 hours. Upon completion of the reaction, the resulting reaction mixture was filtered to remove the by-products. The filtrate was washed sequentially with 1 L of 6N HCl, 1 L of water and 1 L of saturated sodium chloride solution, dried with anhydrous magnesium sulfate, filtered and the solvent was removed by distillation under reduced pressure. The residue was dissolved in 2 L of methanol by heating and cooled to induce crystallization. 2L of water was added and stirred for 30 minutes. The solid was separated by filtration to give 289 g of (4S)-3-[5-(4-fluorophenyl)-1,5-dioxopentyl]-4-phenyl-2-oxazolidinone as a white solid (yield: 86%).1H NMR (300 MHz, CDCl3): δ 7.92 (2H, m), 7.35-7.13 (5H, m), 7.04 (2H, m). 5.43 (1H, q), 4.75 (1H, t), 4.22 (1H, q), 3.05-2.93 (4H, m), 2.03 (2H, m).