Iodine → 2-Chloro-3-fluoro-4-iodopyridine

Participants

Reaction Steps

A solution of lithium di-isopropylamide (2N in tetrahydrofuran/ethylbenzene/heptane, 155 mL, 310 mmol) was added dropwise over 40 minutes to solution of 2-chloro-3-fluoropyridine (31.0 g, 235 mmol) in tetrahydrofuran (200 mL) at −70° C. and the resulting mixture stirred for 4 hours. A solution of iodine (69.0 g, 200 mmol) in tetrahydrofuran (100 mL) was added dropwise over 30 minutes and the resultant mixture was stirred for 30 minutes at −70° C. then allowed to warm to room temperature over 1 hour. The reaction mixture was poured onto aqueous sodium metabisulphite solution (20% w/v, 2 L) and extracted with diethyl ether (3×300 mL). The combined organic extracts were washed with aqueous sodium metabisulphite solution (20% w/v, 2 L) and water (200 mL), dried over Na2SO4 and evaporated under reduced pressure to yield an oil. The resultant oil was triturated with diethyl ether to yield the title compound as a red/brown solid (28 g, 46% yield). 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J=5.0 Hz, 1H), 7.66 (ddd, J=5.0, 4.0, 0.4 Hz, 1H).

Provenance & Evidence