Dimethylformamide → (5-Fluoropyridin-2-yl)methanol

Add butyllithium (10.9 mL, 27.22 mmol, 2.5 M solution in hexanes) to a −78° C. solution of 2-bromo-5-fluoro-pyridine (3.99 g, 22.68 mmol) in toluene (200 mL). Stir the reaction at −78° C. for 90 min and then add N,N-dimethylformamide (2.3 mL, 29.71 mmol) via syringe. Stir the reaction for an additional 2 h at −78° C. and then add sodium borohydride (1.72 g, 45.36 mmol) and allow the reaction to warm to room temperature over a 12 h period. Quench the reaction with saturated aqueous sodium bicarbonate (20 mL) and dilute with ethyl acetate (100 mL). Separate the organic phase and dry (magnesium sulfate), filter and concentrate in vacuo to give a yellow oil. Purify the oil by column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes) to give 1.30 g (45%) as a clear colorless oil. 1H NMR (300 MHz, CDCl3): δ 8.41s, 1H), 7.46-7.37 (m, 1H), 7.32-7.27 (m, 1H), 4.75 (s, 2H), 3.64 (br s, 1H).

1. customthe reaction at −78° C. for 90 min
2. stirringStir
3. customthe reaction for an additional 2 h at −78° C.
4. customthe reaction
5. customQuench
6. customthe reaction with saturated aqueous sodium bicarbonate (20 mL)
7. customSeparate the organic phase
8. dry with materialdry (magnesium sulfate)
9. filtrationfilter
10. concentrationconcentrate in vacuo
11. customto give a yellow oil
12. customPurify the oil by column chromatography (silica gel; 10% to 50% ethyl acetate in hexanes)
13. customto give 1.30 g (45%) as a clear colorless oil

ORD record

ord-af27dffcd1fe40fdaa299c90fc693638

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935722B2