Methyl iodide → 6-Bromo-2-fluoro-3-methylpyridine

Temperature

0 °C

To Diisopropylamine (22.001 mmol; 2240 mg; 3.13 mL) in THF (40 mL) at 0° C. was added N-Butyllithium (2.5 mol/L) in Hexane (24.001 mmol; 9.6 mL). The reaction was stirred at 0° C. for 0.5 h, and then cooled to −78° C. 2-bromo-6-fluoro-pyridine (20.001 mmol; 3520.0 mg) in THF (10 mL) was added dropwise. The mixture was stirred at −78° C. for 3 h. Iodomethane (22.001 mmol; 3122.8 mg; 1.37 mL) was added slowly. The mixture was allowed to warm to room temperature with stirring for 1 hour. The reaction was quenched with water (˜50 mL) and stirred overnight. The layers were separated. The organic layer was concentrated, and the residue was purified on silica eluted with 0 to 5% EtOAc in Heptane to afford 6-bromo-2-fluoro-3-methyl-pyridine as a white solid (2.08 g, 55%).

1. temperaturecooled to −78° C
2. stirringThe mixture was stirred at −78° C. for 3 h
3. temperatureto warm to room temperature
4. stirringwith stirring for 1 hour
5. customThe reaction was quenched with water (˜50 mL)
6. stirringstirred overnight
7. customThe layers were separated
8. concentrationThe organic layer was concentrated
9. customthe residue was purified on silica
10. washeluted with 0 to 5% EtOAc in Heptane

ORD record

ord-ce34054cc8cc4567b96334def5a2e990

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434725B2