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

Temperature

25 °C

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., 1F). m/z (ESI, +ve) 156.2 (M+H)+.

1. temperatureThe resulting mixture was then cooled to 0° C.
2. stirringthe resulting light-yellow solution was stirred at 60° C. for 1.25 h
3. concentrationThe reaction mixture was then partially concentrated in vacuo (to remove THF)
4. custompartitioned between EtOAc (300 mL) and half-saturated aqueous NaHCO3 (100 mL)
5. customThe organic layer separated
6. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
7. washThe combined organic extracts were washed with brine (200 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customChromatographic purification of the residue (silica gel, 0 to 100% EtOAc/hexanes)

ORD record

ord-416fd2507ef64ad4a89a4c88bb7f83ce

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2