Iodine → 3-Fluoro-4-iodopyridine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (50.9 mL, 360 mmol) was added to THF (1600 mL), and the mixture was cooled to 0° C. in an ice bath and then n-butyllithium (137.6 ml, 2.5 M in hexane) was added drop wise at 0° C., and stirred for another 30 minutes. The mixture was then cooled to −78° C., and a solution of 2-cyano-3-fluoropyridine (40 g, 328 mmol) in 300 mL of THF was added. After 25 minutes, a solution of I2 (83.2 g, 328 mmol) in THF (80 mL) was added and the reaction was stirred for 40 minutes at −78° C. The reaction was removed from the cooling bath and quenched with 400 mL sodium thiosulfate solution (10% aq.) followed by water (400 mL). The reaction mixture was diluted with ether (400 mL), and the layers were separated. The organic layer were washed with brine, dried over sodium sulfate, filtered and concentrated to a brown solid. The solid was purified with silica column chromatography eluted with 95:5 hexanes:ethyl acetate to give 3-fluoro-4-iodopicolinonitrile (25.6 g, 31.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.25-8.26 (m, 1H) 8.35 (t, J=5.05 Hz, 1H). MS [M+H] found 249.0.

Provenance & Evidence