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

Participants

Reaction Steps

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).

Provenance & Evidence