Potassium Carbonate → 5-(2,6-difluoro-phenoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

Participants

Reaction Conditions

Reaction Steps

A solution of 5-iodo-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (204 mg, 0.67 mmol) in anhydrous N,N-dimethylformamide (8.5 mL, 0.08M) was treated with 2,6-difluorophenol (0.09 g, 0.69 mmol) and potassium carbonate (0.20 g, 1.45 mmol). The reaction was heated at 120° C. overnight. At this time, the reaction was diluted with water (25 mL) and extracted with methylene chloride (3×25 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (25 mL), dried over magnesium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 24 g, 20% to 40% ethyl acetate/hexanes) afforded 5-(2,6-difluoro-phenoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (99.7 mg, 49%) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.56 (m, 2H), 1.57-1.76 (m, 2H), 1.88-2.01 (m, 1H), 2.01-2.16 (m, 1H), 3.53-3.63 (m, 1H), 3.90-3.98 (m, 1H), 5.82 (dd, J=10.5, 1.6 Hz, 1H), 6.04 (d, J=2.7 Hz, 1H), 7.34-7.43 (m, 2H), 7.43-7.55 (m, 1H), 8.23 (d, J=2.7 Hz, 1H).

Provenance & Evidence