反应详情

温度

50 °C

To a solution of 4-methyl-3-(5-(trifluoromethyl)pyridin-2-yloxy)phenylboronic acid (1.13 g, 0.0038 mol) and tert-butyl 4-(bromomethylene)piperidine-1-carboxylate (871 mg, 0.006 mol) in THF (10.5 mL) was added K3PO4 (2.43 g, 0.011 mol). The flask was put under vacuum and flushed with N2 three times. Water (0.19 mL) was added and the system was flushed with N2 again. PdCl2(dppf) (310 mg, 0.0004 mol) was added and the system was flushed with N2 two to three times again. The reaction mixture was refluxed at 50° C. for 1 h. The reaction mixture was concentrated, diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (2.5% EtOAc-97.5% Hexane) to give the pure title compound (0.50 g). 1H NMR (500 MHz, CDCl3): δ 8.42 (s, 1H), 7.90 (dd, J=2.25 Hz, J=8.75 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.03-6.98 (m, 2H), 6.89 (s, 1H), 6.31 (s, 1H), 3.49 (t, J=5.0 Hz, 2H), 3.40 (t, J=5.5 Hz, 2H), 2.47 (t, J=5 Hz, 2H), 2.30 (s, 3H), 2.13 (s, 3H), 1.46 (s, 9H).

1. customflushed with N2 three times
2. additionWater (0.19 mL) was added
3. customthe system was flushed with N2 again
4. customthe system was flushed with N2 two to three times again
5. concentrationThe reaction mixture was concentrated
6. additiondiluted with water
7. extractionextracted with EtOAc
8. extractionThe organic extract
9. washwas washed with brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by column chromatography (2.5% EtOAc-97.5% Hexane)