反应详情

Under argon atmosphere, a solution of the (S)-isomer-dominant semi-chiral compound (4) of trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid (744.1 g, 0.95 mol) obtained in Step 2 in anhydrous dichloroethane (11.6 L) was added with benzyl alcohol (113.1 g, 1.05 mol), WSC.HCl (200.5 g, 1.05 mol) and DMAP (11.9 g, 98 mmol) under ice cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was added with water (10 L), and the mixture was extracted with chloroform (19 L, 14 L). The organic layer was washed with saturated brine (12 L), dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by column chromatography (silica gel: 28 g, developing solvent: heptane/ethyl acetate=6/1) to obtain a semi-chiral compound (5) of trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid benzyl ester (yellow oil, 745.8 g, yield: 90%).

1. extractionthe mixture was extracted with chloroform (19 L, 14 L)
2. washThe organic layer was washed with saturated brine (12 L)
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customthe resulting residue was purified by column chromatography (silica gel: 28 g, developing solvent: heptane/ethyl acetate=6/1)