反应详情

Potassium hydroxide (1.38 g, 24.63 mmol) was added to a solution of methyl 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.6 g, 2.463 mmol) in methanol (60 mL) and water (20 mL). The reaction mixture was heated to reflux overnight, cooled to room temperature and diluted with water. The methanol was removed under reduced pressure. The residual mixture was acidified to pH 6 with 2N HCl and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to afford 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1.5 g, 96% yield). 1H NMR (400 MHz, DMSO-d6) δ8.82 (s, 1H), 8.03 (s, 1H), 7.91 (t, J=7.91 Hz, 2H), 7.79 (t, J=7.78 Hz, 1H), 7.70 (s, 1H), 5.08 (dt, J=5.93, 11.98 Hz, 1H), 4.11 (br. s., 2H), 3.56 (br. s., 4H), 3.38 (s, 3H), 2.99 (d, J=11.29 Hz, 2H), 2.53-2.59 (m, 1H), 2.42 (br. s., 4H), 2.34 (br. s., 1H), 1.78 (d, J=12.30 Hz, 2H), 1.43 (s, 3H), 1.41 (s, 3H), 1.22-1.39 (m, 3H); MS (m/z) 636.2 (M+H+).

1. temperatureThe reaction 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
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated