反应详情

温度

100 °C

A mixture of 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Part A (62.6 mg, 0.23 mmol), 4-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one Part D of Procedure 9 (50 mg, 0.15 mmol), Potassium phosphate tribasic (65.6 mg, 0.31 mmol), Palladium (II) acetate (1.7 mg, 7.7 μmol), and 2-DICYCLOHEXYLPHOSPHINO-2′,6′-DIMETHOXY-1,1′-BIPHENYL (3.1 mg, 7.72 μmol) in Toluene (1.4 mL) and Water (0.15 mL) was stirred at 100° C. for 16 h. The mixture was filtered, diluted with EtOAc, washed with sat. NaHCO3, dired (MgSO4), and concentrated. The crude was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA to afford 4-(4-(difluoromethoxy)phenyl)-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one B-9 (26.26 mg, 0.057 mmol, 36.7% yield) as a white solid. LC/MS 432 (M+H)+, tR 0.87 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.63 (2H, d), 7.42 (1H, d, J=7.04 Hz), 7.24 (2H, d, J=8.58 Hz), 6.95-7.03 (2H, m), 6.90-6.93 (1H, m), 6.86 (1H, s), 6.48 (1H, d, J=7.26 Hz), 6.40-6.78 (1H, m), 3.88 (3H, s), 3.87 (2H, s), 1.37 (6H, s)

1. filtrationThe mixture was filtered
2. additiondiluted with EtOAc
3. washwashed with sat. NaHCO3, dired (MgSO4)
4. concentrationconcentrated
5. customThe crude was purified