Hydrochloric Acid → [6-(Trifluoromethyl)pyridin-2-yl]methanol

Temperature

-5 °C

To a suspension of 6-trifluoromethylpyridine-2-carboxylic acid (2.53 g, 13.2 mmol) in THF (50 mL) cooled to −5° C. was added triethylamine (1.84 mL, 13.2 mmol) followed by addition of ethyl chloroformate (1.26 mL, 13.2 mmol) and the reaction mixture was stirred for 30 min at 0° C. Lithium borohydride (718 mg, 33 mmol) was added in portions, maintaining the temperature below −5° C. After the addition was complete, the reaction was allowed to warm to room temperature and stirred for 1 h. Temperature was lowered to −5° C. and methanol (10 mL) was added followed by addition of aqueous sodium hydroxide (10 mL, 10%). After the addition of ethyl acetate (50 mL) and water (40 mL), dilute hydrochloric acid was added to obtain pH=5.0. After washing aqueous layer thoroughly with ethyl acetate the combined organic extracts were dried over MgSO4 and concentrated. Purification by flash column (30% EtOAc-Hexane) gave (6-trifluoromethylpyridin-2-yl)methanol (760 mg) as an oil.

1. temperaturemaintaining the temperature below −5° C
2. additionAfter the addition
3. temperatureto warm to room temperature
4. stirringstirred for 1 h
5. customwas lowered to −5° C.
6. additionwas added
7. customto obtain pH=5.0
8. washAfter washing aqueous layer thoroughly with ethyl acetate the combined organic extracts
9. dry with materialwere dried over MgSO4
10. concentrationconcentrated
11. customPurification by flash column (30% EtOAc-Hexane)

ORD record

ord-01daa3de5cca408dadbc468ff70edd5e

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07737300B2