Triethylamine → 2-(Hydroxymethyl)-4-(trifluoromethyl)pyridine

Temperature

0 °C

To a solution of 4-trifluoromethyl-pyridine-2-carboxylic acid (500 mg, 2.62 mmol) in THF (20 mL) at 0° C. was added triethylamine (0.40 mL, 2.88 mmol) followed by ethyl chloroformate (0.28 mL, 2.88 mmol). A thick white precipitate formed. The reaction mixture was stirred at 0° C. for 15 min then a solution of sodium borohydride (297 mg, 7.85 mmol) in water (5 mL) was slowly added via pipet. Vigorous gas evolution was observed and all solids dissolved. The reaction was stirred at 0° C. for 10 min then warmed to room temperature and stirred for 1 h. The reaction was diluted with water and extracted with CH2Cl2 (3×). The combined organics were dried over MgSO4 and concentrated. The residue was purified by chromatography with 20% to 50% EtOAc/hexanes to afford 296 mg (64%) of (4-trifluoromethyl-pyridin-2-yl)-methanol as a colorless oil that freezes just below room temperature. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.76 (d, J=4.9 Hz, 1H), 7.55 (s, 1H), 7.45 (d, J=4.9 Hz, 1H), 4.87 (s, 2H).

1. customA thick white precipitate formed
2. dissolutionall solids dissolved
3. stirringThe reaction was stirred at 0° C. for 10 min
4. temperaturethen warmed to room temperature
5. stirringstirred for 1 h
6. extractionextracted with CH2Cl2 (3×)
7. dry with materialThe combined organics were dried over MgSO4
8. concentrationconcentrated
9. customThe residue was purified by chromatography with 20% to 50% EtOAc/hexanes

ORD record

ord-e984e02dab06411bba68957cde155a32

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2