Acetic Acid → 2,6-Difluorobenzyl alcohol

A stirred solution of 25.0 g (0.158 mole) of 2,6-difluorobenzoic acid in 300 ml of diethyl ether was purged with nitrogen, and 20 ml of a 1 molar solution of borane in tetrahydrofuran was carefully added dropwise. The addition caused the reaction mixture to effervesce. When vigorous effervescence subsided, the reaction mixture was heated to reflux and an additional 170 ml of a 1 molar solution of borane (0.190 mole total) in tetrahydrofuran was added dropwise at a rate just sufficient to promote gentle reflux. Upon complete addition the reaction mixture was heated under reflux for an additional 1 hour, allowed to cool to ambient temperature and stand for 16 hours, then heated under reflux again for 1 hour. Acetic acid (11 ml, 0.19 mole) was added, then the reaction mixture was cooled in an ice-water bath and 100 ml of a saturated aqueous solution of ammonium chloride was added slowly. Upon complete addition the reaction mixture was stirred for 0.5 hour, then concentrated under reduced pressure to give a pasty residue. Diethyl ether was added and the mixture was washed with three portions of water, two portions of aqueous 10% sodium carbonate, two portions of water, and one portion of a saturated aqueous solution of sodium chloride. The organic layer was dried with magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure to give 18.9 g of (2,6-difluorophenyl)methanol as a yellow oil. The nmr spectrum was consistent with the proposed structure.

1. additionwas carefully added dropwise
2. additionThe addition
3. temperaturethe reaction mixture was heated
4. temperatureto reflux
5. additionUpon complete addition the reaction mixture
6. temperaturewas heated
7. temperatureunder reflux for an additional 1 hour
8. temperatureheated
9. temperatureunder reflux again for 1 hour
10. temperaturethe reaction mixture was cooled in an ice-water bath
11. additionUpon complete addition the reaction mixture
12. concentrationconcentrated under reduced pressure
13. customto give a pasty residue
14. washthe mixture was washed with three portions of water, two portions of aqueous 10% sodium carbonate, two portions of water, and one portion of a saturated aqueous solution of sodium chloride
15. dry with materialThe organic layer was dried with magnesium sulfate
16. filtrationfiltered
17. concentrationthe filtrate concentrated under reduced pressure

ORD record

ord-fdc15e5bde7f47ef8b72c4e91f7aa523

Source dataset

uspto-grants-1980_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04238505