反应详情

温度

60 °C

A solution of Example 98B (200 mg, 0.852 mmol), (5-fluoro-2-methoxyphenyl)boronic acid (188 mg, 1.108 mmol), phenylallylchloro[1,3-bis(diisopropylphenyl)-2-imidazol-2-ylidene]palladium(II) (50 mg, 0.077 mmol) and potassium phosphate (543 mg, 2.56 mmol) in 8 mL 3:1 tetrahydrofuran:water was purged with nitrogen and heated under nitrogen at 60° C. for 4 hours. The cooled mixture was diluted with water and ethyl acetate and filtered through diatomaceous earth. The mixture was extracted into ethyl acetate (twice) and the combined extracts were rinsed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (1:1 ethyl acetate:hexanes) provided only a small amount of material. The column was washed with 10% methanol/dichloromethane and the remainder of the material eluted. The combined residue was suspended in diethyl ether and the solids were collected and rinsed with diethyl ether to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ 1.20-1.48 (m, 5H) 1.64-1.76 (m, 3H) 1.99-2.02 (m, 2H) 2.70-2.73 (m, 1H) 3.72 (s, 3H) 5.92 (s, 1H) 6.99 (d, J=5.08 Hz, 1H) 7.15-7.27 (m, 3H) 8.12 (d, J=4.75 Hz, 1H) 11.50 (s, 1H). MS (DCI) m/e 325 (M+H)+.

1. filtrationfiltered through diatomaceous earth
2. extractionThe mixture was extracted into ethyl acetate (twice) and the combined extracts
3. washwere rinsed with brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by flash chromatography (1:1 ethyl acetate:hexanes)
8. customprovided only a small amount of material
9. washThe column was washed with 10% methanol/dichloromethane
10. washthe remainder of the material eluted
11. customthe solids were collected
12. washrinsed with diethyl ether