Potassium Carbonate → Methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 78 mg (0.29 mmol) of methyl 7-bromo-3-quinolinecarboxylate, 97 mg (0.44 mmol) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol, 3 mg (0.01 mmol) of palladium acetate, 8 mg (0.03 mmol) of triphenylphosphine, 218 mg (1.03 mmol) of K3PO4 and 25 μL of H2O in 1.0 mL of dioxane was stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with water and brine then concentrated. To the residue was added 65 mg (0.21 mmol) of 4-(chloromethyl)-3-(2,6-dichlorophenyl)-5-(1-methylethyl)isoxazole, 74 mg (0.54 mmol) of K2CO3 and 1.5 mL of DMF and the mixture was then stirred at 60° C. for 1 hr. EtOAc was added and the organics were washed with three portions of water, then brine. The solution was concentrated and the residue purified by silica gel chromatography (12 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes) to give 47 mg (30%) of methyl 7-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-3-quinolinecarboxylate as a clear glass. 1H NMR (400 MHz, CDCl3): δ 9.44 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 7.96 (d, J=9 Hz, 1H), 7.82 (d, J=9 Hz, 1H), 7.64 (d, J=9 Hz, 2H), 7.41 (d, J=8 Hz, 2H), 7.35-7.31 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.79 (s, 2H), 4.02 (s, 3H), 3.38-3.34 (m, 1H), 1.45 (d, J=7 Hz, 6H). ESI-LCMS m/z 548 (M+H)+.

Provenance & Evidence