Sodium Hydroxide → 6-Bromo-2-fluoropyridin-3-ol

A stirred solution of 2-fluoro-3-pyridinol (1.10 g, 9.73 mmol) and NaOAc (0.80 g, 9.73 mmol) in HOAc (10 mL) was treated with Br2 (1.56 g, 9.73 mmol) at 5° C., and the reaction mixture was allowed to warm to ambient temperature, and stirred at ambient temperature for 4 h. The mixture was poured onto ice and neutralized with 2N NaOH to pH about 7, and then extracted with EtOAc. The combined organic extract was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give a yellow oil. The crude material was purified by flash chromatography on a silica gel column eluted with 1:20 EtOAc/CH2Cl2 to give a colorless oil, which solidified after standing. The solid was recrystallized from hexanes to give 0.2 g (11%) of 6-bromo-2-fluoro-3-pyridinol as a white solid. The filtrate was concentrated to a solid, which was recrystallized from 2:1 hexanes/benzene to give additional 0.57 g (31%) of 6-bromo-2-fluoro-3-pyridinol as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.77 (s, 1H), 7.40-7.30 (m, 2H); LRMS (ESI), m/z 192/194 (M+H).

1. extractionextracted with EtOAc
2. extractionThe combined organic extract
3. washwas washed with water, brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate was concentrated
7. customto give a yellow oil
8. customThe crude material was purified by flash chromatography on a silica gel column
9. washeluted with 1:20 EtOAc/CH2Cl2
10. customto give a colorless oil, which
11. customThe solid was recrystallized from hexanes

ORD record

ord-067ae92f3b3d4bb6a97fd517f5fa58d3

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2