Hydrochloric Acid → (6-Fluoropyridin-3-yl)(4-(methylthio)phenyl)methanol

Participants

Reaction Steps

Magnesium turnings (0.214 g, 8.79 mmol) in a minimal amount of THF were treated with 1,2-dibromoethane (50 μL, cat.) and the mixture was allowed to stand until effervescence was observed (1 min) A solution of 4-bromothioanisole (Aldrich) (1.705 g, 8.39 mmol) in THF (20 mL) was added dropwise and the mixture stirred for 2 h, occasionally heating to gentle reflux with a heat gun, to give a cloudy pale yellow solution. The resulting Grignard solution was added dropwise over 10 min to a solution of 6-fluoronicotinaldehyde (Frontier Scientific) (1.000 g, 7.99 mmol) in THF (10 mL) cooled in a dry ice/acetone bath. The mixture was stirred at −78° C. for 30 min, and then quenched by dropwise addition of 2 N aqueous HCl (9.0 mL, 2 equiv.). The cooling bath was removed and the mixture was allowed to warm to ambient temperature. The mixture was extracted into EtOAc from water, dried (MgSO4) and concentrated to give (6-fluoropyridin-3-yl)(4-(methylthio)phenyl)methanol (1.856 g, 7.44 mmol, 93% yield) as a colorless oil. 1H NMR (400 MHz, d6-DMSO) δ 8.23 (s, 1H); 7.87 (t, J=8.22 Hz, 1H); 7.32 (d, J=8.02 Hz, 2H); 7.22 (d, J=7.82 Hz, 2H); 7.11 (d, J=8.41 Hz, 1H); 6.11 (br. s., 1H); 5.78 (s, 1H); 2.44 (s, 3H). m/z (ESI, +ve) 250.0 (M+H)+.

Provenance & Evidence