2-(Trifluoromethyl)phenylacetonitrile → [5-Chloro-6-oxo-1-(tetrahydro-pyran-2-yl)-1,6-dihydro-pyridazin-4-yl]-(2-trifluoromethyl-phenyl)-acetonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (Intermediate 20, 1.0 g, 4.01 mmol) in tetrahydrofuran (16.7 mL, 0.24M) was treated with (2-trifluoromethyl-phenyl)-acetonitrile (743 mg, 4.01 mmol) followed by potassium tert-butoxide (676 mg, 6.02 mmol). The reaction was heated at 80° C. for 2 h. After this time, the reaction was cooled to 25° C. where it stirred overnight. The reaction mixture was then partitioned between water (100 mL) and methylene chloride (3×75 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 40 g, 20-40% ethyl acetate/hexanes) afforded [5-chloro-6-oxo-1-(tetrahydro-pyran-2-yl)-1,6-dihydro-pyridazin-4-yl]-(2-trifluoromethyl-phenyl)-acetonitrile (0.73 g, 45%) as a yellow solid; ES+-HRMS m/e calcd for C18H15N3O2F3Cl [M+H+] 398.0878, found 398.0878.

Provenance & Evidence