Ammonium Chloride → 3-(2-fluorophenyl)-3-hydroxy-5-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one

Participants

Reaction Conditions

Reaction Steps

16.8 mL of a hexane-cyclohexane solution of 1.0 mol/L sec-butyllithium was added dropwise under −78° C. cooling to a 15 mL tetrahydrofuran solution of 2 g of tert-butyl[4-(trifluoromethyl)phenyl]carbamate, and the reaction mixture was stirred for 1 hour. The temperature was then raised to −40° C., and the reaction mixture was stirred for 2.5 hours at that temperature. The reaction mixture was cooled back down to −78° C., a 7.5 mL tetrahydrofuran solution of 2.23 g of ethyl(2-fluorophenyl)(oxo)acetate was added dropwise, and the reaction mixture was stirred for 2 hours at the same temperature. The temperature was then raised to room temperature, and the reaction mixture was stirred for 12 hours. A saturated ammonium chloride aqueous solution was added to the reaction solution, extraction was performed with ethyl acetate, the organic layer was washed with saturated brine and dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate/hexane=1/1; v/v) to obtain 389 mg of the titled compound (colorless powder).

Provenance & Evidence