Diisopropylamine → 2-Chloro-4-fluoro-3-formylbenzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution (300 mL) of diisopropylamine (12.4 mL) in tetrahydrofuran was added dropwise 1.6 mol/L solution (55.4 mL) of n-butyllithium in hexane at −78° C., and the mixture was stirred at 0° C. for 1 hr. To the prepared lithium diisopropylamide was added dropwise a solution (70 mL) of 2-chloro-4-fluorobenzonitrile (12.0 g) in tetrahydrofuran at −78° C. After the reaction mixture was stirred at the same temperature for 1 hr, N,N-dimethylformamide (6.90 mL) was added thereto. The reaction mixture was stirred for 30 min, and acetic acid (20 mL) was added thereto. The temperature of the mixture was raised to room temperature, saturated brine was added to the mixture and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate=30:1→1:1) and recrystallized from a mixed solvent of isopropyl ether and hexane to give the title compound as a yellow solid (yield: 5.94 g).

Provenance & Evidence