反应详情

温度

10 °C

To a stirred solution of N-biphenyl-4-yl-malonamic acid (0.075 g, 0.0003 mole) in DMF (2 mL) was added, HOBt (0.06 g, 0.00045 mole) and DIPEA (0.135 g, 0.001 mole). The mixture was then cooled to 10° C. and EDCI.HCl (0.086 g, 0.00045 mole) followed by 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (0.073 g, 0.0003 mole) were added. The resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using neutral aluminium oxide (5% methanol in chloroform) to afford 0.03 g (22%) of N-biphenyl-4-yl-3-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionamide. LC-MS purity: 451.18 (M+1)+, 90.58%, 1H NMR (DMSO-d6): δ 10.2 (s, 1H), 7.7 (m, 6H), 7.4 (m, 2H), 7.2 (m, 2H), 6.8 (m, 1H), 4.7 (m, 1H), 3.9 (m, 1H), 3.8 (m, 1H), 3.6 (s, 2H), 3.4 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H).

1. additionwere added
2. extractionthe product was extracted with ethyl acetate
3. dry with materialThe organic layer was dried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by column chromatography