Tetrahydrofuran → 5-(3-Chlorophenylethynyl)-nicotinonitrile

Participants

Reaction Conditions

Reaction Steps

Combine 5-Trimethylsilanylethynyl-nicotinonitrile (3.00 g, 15.0 mmol), (prepared as described in PREPARATION 3), bis(triphenylphosphine)palladium (II) dichloride (526 mg, 0.750 mmol), copper (I) iodide (286 mg, 1.50 mmol), and 3-chloroiodobenzene (2.24 μL, 18.0 mmol) in triethylamine (29.3 mL, 210 mmol). Cool the mixture to −78° C. and add a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (15.3 mL, 15.3 mmol). After 5 min warn to room temperature and stir 72 h. Filter the reaction through diatomaceous earth, washing with ethyl acetate. Concentrate the filtrate and purify by silica gel chromatography, eluting with a gradient from 95:5 to 70:30 (90:10 hexanes:ethyl acetate):dichloromethane. Further purify by silica gel chromatography, eluting with dichloromethane, then 90:10 dichloromethane:ethyl acetate. Dissolve the chromatographed material (2.91 g) in cyclohexane (120 mL) at 80° C. and cool to room temperature. Collect the recrystallized material via vacuum filtration to give the title compound as a white crystalline solid (2.58 g, 72%).

Provenance & Evidence