Methyl iodide → Methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Participants

Reaction Conditions

Reaction Steps

Methyl 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (50 g, 118 mmol) was combined with copper(I) iodide (44.9 g, 236 mmol) and sodium methylsulfinate (24.07 g, 236 mmol) in a 2 L round bottom flask and the vessel was purged with N2 (3×). The solids were suspended in dimethyl sulfoxide (400 mL), the atmosphere was exchanged for nitrogen (3×Vac/N2 purges), and the reaction was heated to 120° C. overnight. The reaction was cooled to 50° C., and iodomethane (50.2 g, 354 mmol) was added. The reaction was stirred for 2 hours at 50° C. and cooled to RT. The crude reaction mixture was added slowly 1 L of water with stirring over 30 minutes. The resulting yellow slurry was filtered through a buchner funnel. The filter cake was washed with 3×500 mL water and dried overnight. The solids were suspended in 625 mL CH2Cl2, and the suspension was stirred for ca. 30 min. The solids were purified by flash chromatography eluting with 100% CH2Cl2→40% EtOAc/CH2Cl2. Fractions containing the product were further purified by trituration with MeOH. Mixed fractions were repurified using the same conditions and combined with the previously isolated solid to provide 31.9 g (64%) of the product as a white solid. MS (m/z) 423.7 (M+H+).

Provenance & Evidence