Iodine → 2-Fluoro-4-iodo-5-(methoxymethoxy)pyridine

Cool a solution of 2-fluoro-5-methoxymethoxy-pyridine (4.1 g, 26.1 mmol) in THF (60 mL) to −75° C. Add tert-butyllithium (1.7 M in pentane, 30.4 mL, 51.7 mmol) over a period of 30 min. Stir the mixture for an additional half an hour. Add iodine (9.8 g, 38.6 mmol, dissolved in 60 mL of THF). Stir for 1 h after the addition is complete. Allow the temperature to raise to RT over 1 h while stirring. Treat the mixture with water. Extract the solution with ethyl acetate three times. Wash the organic layer with aqueous saturated sodium chloride. Dry the mixture over sodium sulfate. Concentrate the solution in vacuo to a brown solid. Triturate the brown solid with hexane. Filter to afford the title compound (3.9 g, 53%) as a brown solid. 1H NMR (400 MHz, CDCl3) δ 3.53 (s, 3H), 5.23 (s, 2H), 7.39 (d, J=4.0 Hz, 1H), 7.96 (d, J=1.6 Hz, 1H).

1. stirringStir for 1 h
2. additionafter the addition
3. stirringwhile stirring
4. extractionExtract the solution with ethyl acetate three times
5. washWash the organic layer with aqueous saturated sodium chloride
6. dry with materialDry the mixture over sodium sulfate
7. concentrationConcentrate the solution in vacuo to a brown solid
8. customTriturate the brown solid with hexane
9. filtrationFilter

ORD record

ord-40618a1aa80c4a0ca16e648ad66047d6

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114872B2