Hydrochloric Acid → 2-Fluoro-4-methyl-5-(trifluoromethyl)benzaldehyde

Temperature

-78 °C

To a −78° C. flask containing THF (7 mL) was added s-BuLi (10 mL of a 1.4 M solution in cyclohexane, 14.0 mmol). To this −78° C. solution was added a solution of 4-fluoro-2-methyl-1-(trifluoromethyl)benzene (2.0 g, 11.23 mmol) in heptanes (7 mL) over 20 minutes. The reaction was stirred at −78° C., for 1 hour and then DMF (1.5 mL) was added. Next, 1N HCl (30 mL) was added, and the reaction was warmed to room temperature and stirred for 10 minutes. The mixture was extracted with hexanes (75 mL) and the organic layer was washed with water and brine (20 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel afforded 2-fluoro-4-methyl-5-(trifluoromethyl)benzaldehyde. Rf=0.44 (15% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 10.31 (s, 1H), 8.14 (d, J=6.6 Hz, 1H), 7.13 (d, J=10.5 Hz, 1H), 2.56 (d, J=1.3 Hz, 3H).

1. temperaturethe reaction was warmed to room temperature
2. stirringstirred for 10 minutes
3. extractionThe mixture was extracted with hexanes (75 mL)
4. washthe organic layer was washed with water and brine (20 mL each)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification of the residue by flash chromatography on silica gel

ORD record

ord-0890746a8f174996a9029ae8b115b31d

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07781426B2