Potassium Hydroxide → 7-(Ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Participants

Reaction Steps

A stirred suspension of methyl 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.3 g, 1.959 mmol) and potassium hydroxide (0.879 g, 15.67 mmol) in methanol (15 mL) and water (3.75 mL) was heated to reflux for 20 h. The mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The resulting yellow oil was partitioned between water and methylene chloride and cooled in an ice bath. The pH was adjusted to ⅚ with 2N HCl and the organic phase was separated. The aqueous phase was extracted twice more with methylene chloride. The combined organic extracts were washed with brine, dried, and concentrated to afford 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1.3 g, 97% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ8.81 (s, 1H), 8.01 (s, 1H), 7.86-7.94 (m, 2H), 7.75-7.82 (m, 1H), 7.67 (s, 1H), 4.37 (q, J=6.80 Hz, 2H), 4.10 (br. s., 2H), 3.84 (quin, J=6.80 Hz, 1H), 3.56 (br. s., 4H), 3.02 (d, J=11.08 Hz, 2H), 2.52-2.63 (m, 2H), 2.44 (br. s., 4H), 2.33 (br. s., 1H), 1.79 (d, J=12.34 Hz, 2H), 1.44 (t, J=6.92 Hz, 3H), 1.26-1.39 (m, 2H), 1.23 (s, 3H), 1.21 (s, 3H); MS (m/z) 650.2 (M+H+).

Provenance & Evidence