Iodine → 3,5-Difluoro-4-iodopicolinonitrile

Participants

Reaction Conditions

Reaction Steps

THF (42 mL) and diisopropylamine (5.6 ml, 39.27 mmol) were combined and cooled at 0° C. then n-butyllithium (17.3 ml, 2.5 M in hexane) was added dropwise at 0° C., and stirred for another 30 minutes. The mixture was then cooled in a dry ice/acetone bath to about −78° C. and a solution of 3,5-difluoropicolinonitrile (5 g, 35.7 mmol) in THF (25 mL) was slowly added. After 30 minutes a solution of I2 (9 g, 35.7 mmol) in THF (35 mL) was added. The reaction was stirred for another 40 minutes at −78° C. in the dry ice/acetone bath, then warmed slightly and quenched with 50 mL sodium thiosulfate solution (10% aq) followed by dilution with water and EtOAc (300 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to a residue which was purified by silica column chromatography eluting with petroleum ether-ethyl acetate (5:1) to give 3,5-difluoro-4-iodopicolinonitrile as a solid (2 g, 21% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1H).

Provenance & Evidence