Methyl iodide → HCID 67418259, compound

Participants

Reaction Conditions

Reaction Steps

6-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (90 g, 258 mmol) was treated with KOH (14.48 g, 258 mmol) in water. The solution was concentrated and azeotroped with toluene (three times). The resulting solid was dissolved in dimethyl sulfoxide (1 L) and sodium 2-propanethiolate (57.0 g, 581 mmol) was added. The mixture was heated to 100° C. and stirred overnight. The solution was cooled to room temperature and MeI (0.048 L, 774 mmol) was added. After stirring for 1 h, water (500 mL) was added slowly with stirring. The solid precipitate was collected by filtration, washed with water, and dried. The filter cake was dissolved in tetrahydrofuran (1.5 L) and cooled in an ice bath. Oxone (317 g, 516 mmol) was added as a solution in water (1.5 L). The ice bath was removed, and stirring was continued for 2 h. The organic phase was separated, and the aqueous phase was extracted with methylene chloride (three times). The THF and methylene chloride extracts were combined, concentrated to approximately 1 L, diluted with methylene chloride (500 mL), and washed with brine. The organic phase was concentrated to afford a brown residue. Methanol was added and the solution was heated to reflux with stirring. The mixture was cooled to room temperature and stirred overnight. The precipitate was collected by filtration, washed with methanol, and dried under reduced pressure to afford methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (114 g, 97% yield) as an off-white solid. 1H NMR (400 MHz, METHANOL-d4) 68.29-8.36 (m, 2H), 8.17 (d, J=8.78 Hz, 1H), 7.97 (s, 1H), 7.91 (d, J=7.53 Hz, 1H), 7.85 (d, J=7.78 Hz, 1H), 7.76 (t, J=7.78 Hz, 1H), 4.13 (s, 3H), 3.47 (quin, J=6.71 Hz, 1H), 2.45 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H); MS (m/z) 452.1 (M+H+).

Provenance & Evidence