反应详情

温度

10 °C

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.075 g, 0.00029 mole) in DMF (2.0 mL) was added HOBt (0.042 g, 0.00031 mole) and DIPEA (0.083 g, 0.00065 mole). The mixture was cooled to 10° C. and EDCI.HCl (0.060 g, 0.00031 mole) followed by 4-(2-bromo-phenoxy)-piperidin-1-ylamine trifluoroacetate (0.106 g, 0.00029 mole) were added. The mixture was stirred at the ambient temperature overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The organic layer was washed with brine and concentrated. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (40% ethyl acetate in hexane) to afford 0.045 g (31%) of N-biphenyl-4-yl-3-[4-(2-bromo-phenoxy)-piperidin-1-yl]-3-oxo-propionamide. LCMS: 493 (M+1)+, 94.19%, 1H NMR (CDCl3): δ 10.0 (s, 1H), 7.66 (d, 2H), 7.58 (m, 5H), 7.44 (t, 2H), 7.32 (m, 1H), 6.9 (m, 2H), 4.52 (m, 1H), 4.15 (m, 1H), 3.56 (m, 1H), 3.54 (m, 2H), 3.51 (d, 2H), 2.0 (m, 2H), 1.8 (m, 2H).

1. additionwere added
2. extractionthe product was extracted with ethyl acetate
3. washThe organic layer was washed with brine
4. concentrationconcentrated
5. customThe resulting residue was purified by column chromatography