反应详情

温度

100 °C

Sodium hydride (0.949 g, 23.73 mmol) was added portionwise to a suspension of 6-fluoro-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (6.0 g, 15.82 mmol) in dimethyl sulfoxide (50 mL). After 20 min, sodium thiomethoxide (1.44 g, 17.40 mmol) was added. The reaction mixture was heated to 100° C. for 2 h. The mixture was cooled to room temperature and iodomethane (4.95 mL, 79 mmol) was added. The reaction mixture was stirred for 2 h, diluted with ether, and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (2 times), dried over Na2SO4, filtered, and concentrated. The residue was purified via column chromatography (ISCO, 330 g silica, 0-15% ethyl acetate/hexanes) to give methyl 3-methyl-7-(methyloxy)-6-(methylthio)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (5.48 g, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.94-8.01 (m, 2H), 7.87 (d, J=7.28 Hz, 1H), 7.77 (d, J=7.53 Hz, 1H), 7.49 (s, 1H), 7.24 (s, 1H), 4.07 (s, 3H), 4.01 (s, 3H), 2.53 (s, 3H), 2.34 (s, 3H); MS (m/z) 422.1 (M+H+).

1. temperatureThe mixture was cooled to room temperature
2. extractionextracted with methylene chloride (three times)
3. washThe combined organic extracts were washed with brine (2 times)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified via column chromatography (ISCO, 330 g silica, 0-15% ethyl acetate/hexanes)