2-(Trifluoromethyl)pyridine-3-carboxylic acid → [2-(Trifluoromethyl)pyridin-3-yl]methanol

(2-(2-(Trifluoromethyl)pyridin-3-yl)methanol (I-29A). A solution of 2-(trifluoromethyl)nicotinic acid (5 g, 26.2 mml) in dry tetrahydrofuran (50 mL) was cooled to −10° C. and then treated with LiAlH4 (39 mL, of a 1M solution in THF) by very slow addition. The reaction mixture was stirred at room temperature for 14 hours. The reaction was then cooled to −10° C. and quenched with a very slow dropwise addition of water (2 mL) and 6N HCl (1.2 mL). The reaction mixture was further diluted with water and extracted with dietyl ether (3×100 mL). The organics were combined and washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude oily residue was purified by silica gel chromatography with a gradient of 0-10% ethyl acetate-dichloromethane to yield (2-(trifluoromethyl)pyridin-3-yl)methanol (I-29A) as pale yellow oil. 1H-NMR (400 MHz, CDCl3) δ 8.61 (d, J=4.8 Hz, 1H), 8.15 (dd, J=8.0, and 0.8 Hz, 1H), 7.55 (dd, J=8.0 and 4.4 Hz, 1H), 4.95 (d, J=6.0 Hz, 2H), 2.02 (t, J=6.0 Hz, 1H). MS m/z 178.0 (M+1).

1. temperatureThe reaction was then cooled to −10° C.
2. customquenched with a very slow dropwise addition of water (2 mL) and 6N HCl (1.2 mL)
3. additionThe reaction mixture was further diluted with water
4. extractionextracted with dietyl ether (3×100 mL)
5. washwashed with brine
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe crude oily residue was purified by silica gel chromatography with a gradient of 0-10% ethyl acetate-dichloromethane

ORD record

ord-9a71d77a51144ee89ca1a38af9e01efe

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150568B2