Diethyl Ether → (6-Bromo-3-fluoropyridin-2-yl)methanol

Temperature

0 °C

Slowly add n-Butyllithium (2.5 M in hexanes, 9.40 mL, 23.3 mmol) to a −78° C. solution of 2-bromo-5-fluoro-pyridine (3.42 g, 19.4 mmol) and diethyl ether (200 mL). Stir the reaction at −78° C. for 1 h, then add dimethylformamide (2.00 mL, 25.5 mmol) and continue stirring for an additional hour. Warm the reaction to room temperature and remove the solvent under vacuum. Dissolve the crude material in methanol (50 mL) and cool to 0° C. Add sodium borohydride.(1.47 g, 38.9 mmol) and allow the reaction is to slowly warm to room temperature over 12 h. Quench the reaction with saturated aqueous sodium bicarbonate (20 mL) then add ethyl acetate (100 mL). Separate the layers and dry the resultant organic layer with magnesium sulfate, filter, and concentrate under vacuum to give a yellow solid. Purify the crude solid by column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes) to give 1.66 g (42%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 7.50-7.40m, 1H), 7.35-7.25 (m, 1H), 4.80 (s, 2H), 3.30 (s, 1H).

1. customto a −78° C.
2. customthe reaction at −78° C. for 1 h
3. temperatureWarm
4. customthe reaction to room temperature
5. customremove the solvent under vacuum
6. dissolutionDissolve the crude material in methanol (50 mL)
7. temperatureto slowly warm to room temperature over 12 h
8. customQuench
9. customthe reaction with saturated aqueous sodium bicarbonate (20 mL)
10. customSeparate the layers
11. dry with materialdry the resultant organic layer with magnesium sulfate
12. filtrationfilter
13. concentrationconcentrate under vacuum
14. customto give a yellow solid
15. customPurify the crude solid by column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes)

ORD record

ord-612b0e066c144ea184f715baeca9ffb0

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935722B2