反应详情

温度

50 °C

To a solution of tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (1.1 g, 0.0039 mol) in THF (13 mL) was added 3-fluoro-5-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid (1.4 g, 4.7 mmol), potassium phosphate (2.5 g, 0.012 mol) and H2O (0.23 mL) and the mixture was degassed using argon. PdCl2(dppf)2 (0.32 g, 0.4 mmol) was added and the mixture was degassed again. The reaction was heated at 50° C. for 1.5 h and then allowed to cool to RT. Water was added and the mixture was extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography (2-4% ethyl acetate in hexane) to give the title compound (0.585 g, 19%). 1H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.05 (d, J=8.65 Hz, 1H), 6.81-6.75 (m, 3H), 6.30 (s, 1H), 3.51 (t, J=5.55 Hz, 2H), 3.42 (t, J=5.6 Hz, 2H), 2.47 (t, J=5.55 Hz, 2H), 2.33 (m, 2H), 1.47 (s, 9H).

1. customthe mixture was degassed
2. customthe mixture was degassed again
3. temperatureto cool to RT
4. additionWater was added
5. extractionthe mixture was extracted with ethyl acetate three times
6. washThe organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. customevaporated to dryness
9. customThe residue was purified by silica gel column chromatography (2-4% ethyl acetate in hexane)