Hydrogen Peroxide → 2-(6-Fluoropyridin-3-yl)propan-1-ol

Participants

Reaction Conditions

Reaction Steps

Borane tetrahydrofuran complex (1.0M in THF) (Aldrich, St. Louis, Mo.; 15.75 mL, 15.75 mmol) was added to a solution of 2-fluoro-5-(prop-1-en-2-yl)pyridine (1.44 g, 10.50 mmol) in THF (70 mL) at 0° C. and the resulting mixture was stirred under argon at 25° C. for 1.5 h. The resulting mixture was then cooled to 0° C., and sodium hydroxide (2.5N, aqueous; 5.25 mL, 13.12 mmol) and hydrogen peroxide (30%, aq.) (Columbus Chemical Industries, Columbus, Wis.; 1.877 mL, 18.37 mmol) were sequentially added (gas evolution), and the resulting light-yellow solution was stirred at 60° C. for 1.25 h. The reaction mixture was then partially concentrated in vacuo (to remove THF) and partitioned between EtOAc (300 mL) and half-saturated aqueous NaHCO3 (100 mL). The organic layer separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with brine (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0 to 100% EtOAc/hexanes) furnished 2-(6-fluoropyridin-3-yl)propan-1-ol (0.951 g, 6.13 mmol, 58.4% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J=2.0 Hz, 1H), 7.68 (td, J=8.0, 2.5 Hz, 1H), 6.90 (dd, J=8.4, 2.9 Hz, 1H), 3.67-3.79 (m, 2H), 3.00 (sxt, J=6.8 Hz, 1H), 1.31 (d, J=7.0 Hz, 3H). 19F NMR (377 MHz, CDCl3) δ ppm −71.31 (br. s., 1 F). m/z (ESI, +ve) 156.2 (M+H)+.

Provenance & Evidence