反应详情

温度

80 °C

A flask was charged with 3-Bromomethyl-3′-chloro-2-fluoro-6-methoxy-biphenyl (I-32, 3.3 g, 10 mmol), 2-fluoro-pyridine-5-boronic acid (1.4 g, 10 mmol), toluene (40 mL), 2M aq. Na2CO3 (10 mL, 20 mmol), ethanol (10 mL) and Pd(PPh3)4 (577 mg, 0.5 mmol). The reaction mixture was bubbled with nitrogen gas for 5 minutes. Then the yellow reaction mixture was stirred at 80° C. After overnight stirring the reaction mixture was cooled to room temperature and concentrated in-vacuo. The residue was diluted in EtOAc (20 mL) and washed with water (30 mL). The aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and concentrated in-vacuo. The crude was purified by silica gel column chromatography, eluted with hexane/EtOAc (9:1) to produce 3.23 g (93% yield) of 5-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (P-456) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) 3.73 (s, 3H), 3.98 (s, 2H), 6.95 (d, J=8.6 Hz, 1H), 7.11 (dd, J=8.4, 2.8 Hz, 1H), 7.25-7.51 (m, 5H), 7.82 (td, J=8.2, 2.4 Hz, 1H), 8.14 (s, 1H), 8.32 (s, 1H) ppm.

1. customThe reaction mixture was bubbled with nitrogen gas for 5 minutes
2. stirringAfter overnight stirring the reaction mixture
3. temperaturewas cooled to room temperature
4. concentrationconcentrated in-vacuo
5. additionThe residue was diluted in EtOAc (20 mL)
6. washwashed with water (30 mL)
7. extractionThe aqueous layer was extracted with EtOAc (2×20 mL)
8. washThe combined organic layers were washed with brine (50 mL)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in-vacuo
11. customThe crude was purified by silica gel column chromatography
12. washeluted with hexane/EtOAc (9:1)