Iodine → 5-Cyclopropyl-2-fluoro-3-iodopyridine

Participants

Reaction Steps

Cool a solution of 5-cyclopropyl-2-fluoro-pyridine (1.3 g, 9.5 mmol) in THF (20 mL) to −75° C. in a dry ice-acetone bath under nitrogen. Add lithium diisopropylamide (2 M in THF, 6 mL, 12 mmol) over a period of 30 min. Stir the mixture for an additional 3 hours. Add iodine (2.9 g, 11.4 mmol, dissolved in 50 mL of THF) and stir the mixture for 2 hours. Add water (100 mL) and allow the temperature to rise to room temperature over 1 hour while stirring. Treat the mixture with saturated aqueous sodium thiosulfate solution (50 mL). Extract the solution with ether. Concentrate the solution in vacuo to brown oil. Purify by column chromatography (hexane to 20% ethyl acetate in hexane) to afford the title compound (1.7 g, 68%) as a yellow oil. 1H NMR (400 MHz-CDCl3) δ 8.03 (dd, J=3, 8 Hz, 1H), 7.99 (s, 1H), 0.91-1.00 (m, 2H), 0.71-0.78 (m, 2H).

Provenance & Evidence