Iodine → 2,6-Difluoro-3-iodopyridine

Participants

Reaction Steps

To a solution of butyllithium (38.8 ml, 97 mmol) in tetrahydrofuran (194 ml) at −78° C. was added diisopropylamine (13.8 ml, 97 mmol) dropwise. After 15 minutes at −78° C., 2,6-difluoropyridine (8.8 ml, 97 mmol) was added slowly. After 1 hour slowly, a solution of iodine (24.6 g, 97 mmol) in tetrahydrofuran (50 ml) was carefully added, keeping the internal temperature at −78° C. Sodium sulfite (3.0 g, 24 mmol) was added and the temperature was allowed to gradually increase to ambient temperature. The reaction mixture was diluted with ethyl ether, washed with water, then dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel, eluting (ethyl acetate/isohexane gradient) to give 2,6-difluoro-3-iodopyridine.

Provenance & Evidence