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

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).

1. additionwas then added (dropwise),
2. dissolutionto dissolve the precipitate
3. customthe organic layer was separated
4. extractionThe aqueous layer was extracted with DCM (2×150 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-be505a639ebe407a87e0b0a55da89566

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2