Dimethylformamide → 5-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

Participants

Reaction Conditions

Reaction Steps

Cesium fluoride (570 mg, 3.8 mmol), tetrakis(triphenylphosphine)palladium(0) (220 mg, 0.19 mmol), and copper(I) iodide (72 mg, 0.38 mmol) were added to a solution of 5-fluoro-2-iodo-4-(trifluoromethyl)phenol (Preparation 885, 579 mg, 1.89 mmol) and 4-(tributylstannyl)pyridazine (770 mg, 2.1 mmol) in N,N-dimethylformamide (4 mL, 50 mmol). The sides of the flask were washed down with N,N-dimethylformamide (3 mL, 40 mmol). The flask was capped with a septum then evacuated and back-filled with argon (5 cycles). The reaction mixture was heated at 45° C. After 90 min, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and water, and filtered through diatomaceous earth. The solids were washed with additional ethyl acetate. The layers were separated, and the organic layer was washed successively with water, aqueous lithium chloride, and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (24 g SiO2, methylene chloride to 9:1 methylene chloride-methanol) to afford the product as a tan solid (305 mg, 62%).

Provenance & Evidence