Methanol → 1-(6-Fluoropyridin-3-yl)ethan-1-ol

Participants

Reaction Steps

A clear solution (prepared by filtration of a slightly cloudy suspension) of 6-fluoronicotinaldehyde (Frontier Scientific, Logan, Utah; 9.88 g, 79 mmol) in THF (100 mL) was added dropwise via addition funnel to a solution of methylmagnesium bromide (3.0 M in diethyl ether; 31.6 mL, 95 mmol) in THF (280 mL) at −6° C. (Addition was completed over about 20 min; reaction temperature kept below −5° C. during addition.) MeOH (10 mL) was then added (dropwise), followed by saturated aqueous NH4Cl (300 mL) and sufficient water to dissolve the precipitate. EtOAc (200 mL) was then added, and the organic layer was separated. The aqueous layer was extracted with DCM (2×150 mL), and all organic extracts were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 1-(6-fluoropyridin-3-yl)ethanol (10.55 g, 95% yield) as a light-yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=2.0 Hz, 1H) 7.85 (td, J=8.1, 2.5 Hz, 1H) 6.92 (dd, J=8.5, 2.8 Hz, 1H) 4.98 (q, J=6.5 Hz, 1H) 2.21 (br. s., 1H) 1.53 (d, J=6.5 Hz, 3H).

Provenance & Evidence