Triphenylphosphine → 4-[1-(4-Fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-2-methyl-pyridine

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Reaction Steps

4-Iodo-2-methyl-pyridine (656 mg, 3.0 mmol) was dissolved in 10 mL dry THF and 10 mL piperidine. This mixture was evacuated and backfilled with argon several times to remove oxygen from the solution. Triphenylphosphine (20 mg, 0.07 mmol) and bis(triphenylphosphin)palladium(II)chloride (175 mg, 0.10 mmol) were added and the reaction mixture was stirred at RT for 1 h. Copper(I)iodide (14 mg, 0.07 mmol) and 4-ethynyl-1-(4-fluoro-phenyl)-2-methyl-1H-imidazole (IV-1) (500 mg, 2.5 mmol) were added. The reaction mixture was then refluxed for 3 h. The solvent was evaporated. The residue was taken up in 30 mL water and extracted three times with ethyl acetate (50 mL each). The combined organic extracts were dried with magnesium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol 100:0→90:10 gradient) and recrystallization from diethylether and the desired product was obtained as a light yellow solid (250 mg, 34%), mp=151° C., MS: m/e=292.1 (M+H+).

Provenance & Evidence