Methyl iodide → 2-Fluoro-4-iodo-3-methylpyridine

n-Butyl lithium (1.6M hexane solution, 53.8 mL) was added to a solution of diisopropylamine (8.71 g) in THF (200 mL) at −10 C. After being stirred at the same temperature under nitrogen atmosphere for 1 hour, a solution of 2-fluoro-3-iodopyridine (18.3 g) in THF (70 mL) was added to the reaction mixture at −78 C. The mixture was stirred at the same temperature under nitrogen atmosphere for 1 hour. A solution of iodomethane (12.8 g) in THF (30 mL) was added to the reaction mixture at −78 C. The mixture was stirred at the same temperature under nitrogen atmosphere for 2 hours. The mixture was quenched with aqueous saturated ammonium chloride solution at 0 C and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was passed through NH-silica and concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to give the title compound (17.2 g).

1. stirringThe mixture was stirred at the same temperature under nitrogen atmosphere for 1 hour
2. stirringThe mixture was stirred at the same temperature under nitrogen atmosphere for 2 hours
3. customThe mixture was quenched with aqueous saturated ammonium chloride solution at 0 C
4. extractionextracted with ethyl acetate
5. customThe organic layer was separated
6. washwashed with water and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated in vacuo
9. concentrationconcentrated in vacuo
10. customThe residue was purified by a silica gel column chromatography (hexane/ethyl acetate)

ORD record

ord-cdb63a68c14a40979644f5f50ef0a57c

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09120777B2