Potassium Hydroxide → 7-[(1-Methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245187Notes

Reaction equation

HRID 245187 reaction equation
[OH-].[K+].[CH3:3][CH:4]([O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([C:40]([O:42]C)=[O:41])=[C:12]([CH2:27][N:28]3[CH2:33][CH2:32][CH:31]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:30][CH2:29]3)[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=3)=[N:14]2)=[CH:9][C:8]=1[S:44]([CH3:47])(=[O:46])=[O:45])[CH3:5]>CO.O>[CH3:5][CH:4]([O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([C:40]([OH:42])=[O:41])=[C:12]([CH2:27][N:28]3[CH2:29][CH2:30][CH:31]([N:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:32][CH2:33]3)[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:24])[F:25])[CH:18]=3)=[N:14]2)=[CH:9][C:8]=1[S:44]([CH3:47])(=[O:46])=[O:45])[CH3:3]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 67417428Methyl 7-[(1-methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 674183557-[(1-Methylethyl)oxy]-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 96%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-a2125244b653474bb4c0377f877f5358
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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