反应详情

Potassium hydroxide (1.805 g, 32.2 mmol) was added to a solution of methyl 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.09 g, 3.22 mmol) in methanol (60 mL) and water (20 mL). The mixture was heated to reflux overnight, cooled to room temperature, and diluted with water. The methanol was removed under reduced pressure, and the remaining aqueous solution was acidified to pH 6 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated in vacuo to afford 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1.82 g, 89% yield). 1H NMR (400 MHz, DMSO-d6) ™ 8.80 (s, 1H), 8.03 (s, 1H), 7.88-7.94 (m, 2H), 7.76-7.82 (m, 1H), 7.67 (s, 1H), 4.37 (q, J=6.94 Hz, 2H), 4.08 (br. s., 2H), 3.50-3.62 (m, 6H), 2.99 (br. s., 2H), 2.31-2.59 (m, 6H), 1.79 (d, J=12.30 Hz, 2H), 1.45 (t, J=6.90 Hz, 3H), 1.23-1.41 (m, 3H), 1.14 (t, J=7.40 Hz, 3H); MS (m/z) 636.2 (M+H+).

1. temperatureThe mixture was heated
2. temperatureto reflux overnight
3. customThe methanol was removed under reduced pressure
4. extractionextracted with methylene chloride (three times)
5. washThe combined organic extracts were washed with brine (two times)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo