Diisopropylamine → 4-Fluoro-5-formyl-2-(trifluoromethyl)benzonitrile

Participants

Reaction Steps

To a solution (75 mL) of diisopropylamine (3.89 mL) in tetrahydrofuran was added dropwise 1.6 mol/L solution (17.30 mL) of n-butyllithium in hexane at 0° C., and the mixture was stirred for 30 min. To the prepared lithium diisopropylamide was added dropwise a solution (25 mL) of 4-fluoro-2-(trifluoromethyl)benzonitrile (3.00 g) in tetrahydrofuran at −78° C., and the mixture was stirred at the same temperature for 20 min. N,N-Dimethylformamide (2.14 mL) was added thereto. The reaction mixture was stirred for 15 min, and acetic acid (4 mL) was added thereto. After the temperature of the reaction mixture was raised to room temperature, saturated brine was added to the mixture and the mixture was extracted with ethyl acetate. The extract was washed with 1 mol/L hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=15:1→1:1) to give a mixture (2.30 g) of the title compound and 4-fluoro-3-formyl-2-(trifluoromethyl)benzonitrile (3:1) as a yellow oil.

Provenance & Evidence