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

HRID 245208Notes

Reaction equation

HRID 245208 reaction equation
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([C:37]([O:39]C)=[O:38])=[C:9]([CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:27][CH2:26]3)[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:11]2)=[CH:6][C:5]=1[S:41]([CH:44]([CH3:46])[CH3:45])(=[O:43])=[O:42])[CH3:2].[OH-].[K+]>CO.O>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([C:37]([OH:39])=[O:38])=[C:9]([CH2:24][N:25]3[CH2:26][CH2:27][CH:28]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:29][CH2:30]3)[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=3)=[N:11]2)=[CH:6][C:5]=1[S:41]([CH:44]([CH3:45])[CH3:46])(=[O:43])=[O:42])[CH3:2]

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 67418887Methyl 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 674183257-(Ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 102.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 20 h
  3. customthe solvent was removed under reduced pressure
  4. customThe resulting yellow oil was partitioned between water and methylene chloride
  5. temperaturecooled in an ice bath
  6. customthe organic phase was separated
  7. extractionThe aqueous phase was extracted twice more with methylene chloride
  8. washThe combined organic extracts were washed with brine
  9. customdried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b80fb62be907486db35fe5ccf84a0c60
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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