Hydrochloric Acid → 6-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Participants

Reaction Steps

5-Fluoroisatin (61.3 g, 371 mmol) was dissolved in ethanol (564 mL) to provide a dark red solution. KOH (125 g, 2226 mmol) was dissolved in water (226 mL) and the solution was added slowly to the isatin solution. 1-[3-(Trifluoromethyl)phenyl]-1-propanone (75 g, 371 mmol) was added, and the solution was heated to reflux for 1 h. The reaction mixture was cooled in an ice bath and neutralized with concentrated HCl (208 mL, 2597 mmol). The precipitate was collected by filtration, washed with water (100 mL), and air dried. The solid material was crushed and resuspended in 1:1 ethanol/water (800 mL). The slurry was refluxed for 30 min. The solid was collected by filtration, washed with 1:1 ethanol/water (100 mL), and dried. The solid material was crushed and resuspended in 1:1 ethanol/water (800 mL). The slurry was refluxed for 30 min. The solid was collected by filtration, washed with 1:1 ethanol/water (100 mL), and dried in a vacuum oven at 50° C. for 6 h to afford 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (118.3 g, 91% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 14.41 (br. s., 1H), 8.19 (dd, J=5.65, 9.16 Hz, 1H), 7.94-8.00 (m, 2H), 7.89 (d, J=8.03 Hz, 1H), 7.72-7.81 (m, 2H), 7.53 (dd, J=2.76, 9.79 Hz, 1H), 2.41 (s, 3H); MS (m/z) 350.1 (M+H+).

Provenance & Evidence