8-Hydroxyquinoline → 4-(1-(4-(Trifluoromethoxy)phenyl)-1H-pyrazol-3-yl)benzoic acid

Participants

Reaction Steps

Methyl 4-(1H-pyrazol-3-yl)benzoate (2.00 g, 9.89 mmol), 1-bromo-4-(trifluoromethoxy)benzene (2.38 g, 9.88 mmol), copper (I) iodide (0.28 g, 1.47 mmol), 8-hydroxyquinoline (0.21 g, 1.45 mmol), and cesium carbonate (6.47 g, 19.86 mmol) in DMF/water (11:1) was heated at 120° C. for 20 hours. The reaction was cooled, diluted with water and EtOAc, and decanted from the copper solids. The mixture was extracted three times with EtOAc (3×150 mL) and the combined organic layers washed with water. The organic layers were dried over anhydrous sodium sulfate, filtered, and adsorbed onto silica gel. Purification by flash chromatography (0-10% MeOH/dichloromethane) gave 4-(1-(4-(trifluoromethoxy)phenyl)-1H-pyrazol-3-yl)benzoic acid as a brown solid (580 mg, 16%): 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J=7.7 Hz, 2H), 8.03 (d, J=7.7 Hz, 2H), 7.98 (d, J=2.5 Hz, 1H), 7.85-7.79 (m, 2H), 7.35 (d, J=8.4 Hz, 2H), 6.88 (d, J=2.5 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −58.05; ESIMS m/z 349 ([M+H]+).

Provenance & Evidence