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

HRID 245198Notes

Reaction equation

HRID 245198 reaction equation
[OH-].[K+].[CH3:3][CH:4]([S:6]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[C:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1)[C:13]([CH2:31][N:32]1[CH2:37][CH2:36][CH:35]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH2:34][CH2:33]1)=[C:12]2[C:44]([O:46]C)=[O:45])(=[O:8])=[O:7])[CH3:5]>CO.O>[CH3:5][CH:4]([S:6]([C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[C:14]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1)[C:13]([CH2:31][N:32]1[CH2:37][CH2:36][CH:35]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH2:34][CH2:33]1)=[C:12]2[C:44]([OH:46])=[O:45])(=[O:8])=[O:7])[CH3:3]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 67417230Methyl 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 674194216-[(1-Methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 89%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Potassium hydroxide (0.665 g, 11.85 mmol) was added to a solution of methyl 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (0.77 g, 1.185 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, and the residue was acidified to about pH 6 with 2N HCl and extracted with methylene chloride (three times). The combined organic extracts were washed twice with brine, dried over Na2SO4, filtered, and concentrated to afford 6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.67 g, 89% yield). 1H NMR (400 MHz, DMSO-d6) δ8.81 (s, 1H), 8.03 (s, 1H), 7.91 (t, J=6.53 Hz, 2H), 7.76-7.82 (m, 1H), 7.70 (s, 1H), 4.05-4.12 (m, 5H), 3.81 (dt, J=6.87, 13.61 Hz, 1H), 3.57 (br. s., 4H), 3.01 (d, J=9.79 Hz, 2H), 2.41-2.49 (m, 4H), 2.31-2.40 (m, 1H), 1.78 (d, J=11.54 Hz, 2H), 1.24-1.41 (m, 4H), 1.22 (s, 3H), 1.20 (s, 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 twice with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-55c6bb2c984c4e66980b195e0757b722
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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