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

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) during a period of 30 min. Stir the mixture for another 3 h before adding iodine (2.9 g, 11.4 mmol, dissolved in 50 mL of THF). Keep stirring for 2 more hours before adding water (100 mL) to the mixture. Then allow to warm to RT during 1 h under stirring. Treat the mixture with a saturated sodium thiosulfate solution (50 mL). Extract the solution with ether. Concentrate the solution in vacuo. Purify by column chromatography (hexane→20% ethyl acetate in hexane) to afford the title compound as a yellow oil (1.7 g, 68%). 1H NMR (400 MHz-CDCl3) δ 7.99 (d, J=3 Hz, 1H), 7.39 (td, J=3, 5 Hz, 1H), 6.79 (dd, J=3, 8 Hz, 1H), 0.96-1.02 (m, 2H), 0.63-0.69 (m, 2H).

1. stirringKeep stirring for 2 more hours
2. stirringunder stirring
3. extractionExtract the solution with ether
4. concentrationConcentrate the solution in vacuo
5. customPurify by column chromatography (hexane→20% ethyl acetate in hexane)

ORD record

ord-482c9b9a54fa4e83858709792f5948b0

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114872B2