Diisopropylamine → 1-(5-Bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-one

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of diisopropylamine (56.4 g, 0.55 mol) in THF (500 mL) at −40° C., n-butyl lithium (200 mL, 2.66 M hexane solution) was added dropwise. The mixture was stirred at −40° C. for 1 hour and then cooled to −78° C. Then, a solution of 4-fluorobromobenzene (87.5 g, 0.50 mol) in THF (100 mL) was slowly added dropwise thereto such that the inner temperature of the reaction solution did not exceed −70° C. After the reaction solution was stirred at −78° C. for 1 hour, a solution of ethyl trifluoroacetate (65.4 mL, 0.55 mol) in THF (100 mL) was added thereto at the same temperature. After the temperature of the reaction solution was raised to 0° C. over 1 hour under stirring, a saturated aqueous ammonium chloride solution was added thereto, and the solution was diluted with ethyl acetate. The organic layer was separated and washed with saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/4), and the resulting yellow oily substance was purified again by distillation under reduced pressure (1 mmHg, 53° C.), whereby the objective compound (83.8 g, 61.8%) was obtained as a yellow oily substance.

Provenance & Evidence