反应详情

To a stirred mixture of 6-fluoro-1-isopropyl-1,3-dihydro-2H-benzimidazol-2-one (Step 2 of Example 9, 0.58 g, 3 mmol) and p-nitrophenylchloroformate (0.66 g, 3.3 mmol) in dichloromethane (15 mL) was added triethylamine (1.25 mL, 9.0 mmol) at room temperature. After being stirred for 2 h, a solution of 4-{[4-(aminomethyl)piperidin-1-yl]methyl}tetrahydro-2H-pyran-4-ol (Step 2 of Example 1, 0.75 g, 3.3 mmol) in dichloromethane (15 mL) was added to the mixture. After being stirred for 4 h, the mixture was diluted with ethyl acetate (100 mL). Then, the organic layer was washed with 0.5 N NaOH aq. (10 mL) for 5 times and brine, dried over MgSO4 and concentrated. The residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (3:1) to give 0.97 g (79%) of the title compound as a white solid.

1. stirringAfter being stirred for 4 h
2. washThen, the organic layer was washed with 0.5 N NaOH aq. (10 mL) for 5 times and brine
3. dry with materialdried over MgSO4
4. concentrationconcentrated
5. customThe residue was chromatographed on a column of aminopropyl-silica gel eluting with hexane/ethyl acetate (3:1)