Potassium Carbonate → 4-chloro-2-(tetrahydro-pyran-2-yl)-5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one

Participants

Reaction Conditions

Reaction Steps

A solution of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (4.00 g, 16.05 mmol) (Intermediate 20) in acetonitrile (178 mL, 0.09M) was treated with potassium carbonate (2.21 g, 16.05 mmol) and 2-trifluoromethyl-phenol (2.60 g, 16.05 mmol). The resulting reaction mixture was heated to 105° C. for 18 h and then was allowed to cool to 25° C. The reaction mixture was partitioned between water (150 mL) and methylene chloride (3×100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix) afforded 4-chloro-2-(tetrahydro-pyran-2-yl)-5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one (4.79 g, 79%) as a white solid; ES+-HRMS m/e calcd for C16H14N2O3F3Cl [M+H+] 375.0718, found 375.0718. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.51 (d, 2H), 1.62-1.77 (m, 2H), 1.87-2.12 (m, 2H), 3.55-3.70 (m, 1H), 3.91-4.03 (m, 1H), 5.90 (dd, J=10.4, 2.0 Hz, 1H), 7.45-7.53 (m, 2H), 7.76 (t, J=7.8 Hz, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.91 (s, 1H).

Provenance & Evidence