Methanol → Methyl 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (50 g, 122 mmol) in dichloromethane (700 mL) was cooled to 0° C., and DMF (1.416 mL, 18.28 mmol) was added. To the cooled solution, oxalyl chloride (16.01 mL, 183 mmol) was added dropwise (slowly) and the mixture was stirred at 0° C. for 1 h. Methanol was added and after 2 h the mixture was warmed to room temperature overnight. The solvent was removed under reduced pressure. The residue was treated with water (200 mL) and saturated aqueous NaHCO3 (300 mL) and extracted with methylene chloride (500 mL). The aqueous phase was extracted with methylene chloride (300 mL). The organic phase was washed with saturated aqueous NaHCO3 and brine, dried, filtered, and concentrated. The resulting solid was combined with material from a separate experiment (51 g) and the material was suspended in 400-500 mL of acetonitrile. The mixture was heated to 75° C. until the solid completely dissolved. The mixture was cooled, and the resulting precipitate was collected by filtration and dried. The filtrate was concentrated and the recrystallization procedure was repeated to give additional product. Both batches were combined to afford methyl 6-bromo-3-(methyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (79 g, 73% overall yield). MS (m/z) 426.0 (M+H+).

Provenance & Evidence