Methanesulfonic Acid → 2-Cyclopropyl-4-(4'-fluorophenyl)quinoline-3-carbonitrile

Participants

Reaction Steps

Into a glass flask having an internal volume of 200 mL, equipped with a stirring apparatus, a thermometer, a reflux condenser and a Dean-Stark apparatus, 80 mL of toluene and 20 mL of cyclohexane were put in an atmosphere of nitrogen, and 2.94 g (30.6 mmol) of methanesulfonic acid, 3.50 g (32.1 mmol) of 3-cyclopropyl-3-oxopropanenitrile and 6.59 g (30.6 mmol) of 2-amino-4′-fluorobenzophenone were added thereto with stirring. Then, the temperature was raised, and reaction was carried out at a temperature of from 90 to 95° C. for 4 hours while distilling off the formed water. After completion of the reaction, the reaction liquid was cooled to room temperature, and 100 mL of water and 5.5 mL (44.0 mmol) of 8 mol/L sodium hydroxide aqueous solution were added to make the reaction liquid basic. The obtained reaction liquid was extracted with 200 mL of ethyl acetate twice, then the organic layer was separated, and 2 g of anhydrous magnesium sulfate, 2 g of silica gel and 2 g of activated carbon were added, followed by stirring at room temperature for 1 hour. After filtration, the filtrate was concentrated under reduced pressure to obtain 8.45 g of 2-cyclopropyl-4-(4′-fluorophenyl)quinoline-3-carbonitrile as a pale yellow solid with a purity of 99% (area percentage by high performance liquid chromatography) (yield: 95%).

Provenance & Evidence