Formaldehyde → (6-Bromo-2-fluoropyridin-3-YL)methanol

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 2.5 h. Paraformaldehyde (40.002 mmol; 3603.3 mg) was added rapidly. The mixture was allowed to warm to room temperature and stirred overnight. The reaction was quenched with water. The layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were concentrated and the residue was purified on silica eluted with 0 to 50% EtOAc in Heptane to afford (6-bromo-2-fluoro-3-pyridyl)methanol (1.4888 g, 36%).

1. temperaturecooled to −78° C
2. stirringThe mixture was stirred at −78° C. for 2.5 h
3. temperatureto warm to room temperature
4. stirringstirred overnight
5. customThe reaction was quenched with water
6. customThe layers were separated
7. extractionThe aqueous layer was extracted with EtOAc
8. concentrationThe combined organic layers were concentrated
9. customthe residue was purified on silica
10. washeluted with 0 to 50% EtOAc in Heptane

ORD record

ord-4978cefcf13e4e80a5ca5025f4f3b682

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434725B2