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

HRID 245178Notes

Reaction equation

HRID 245178 reaction equation
[OH-].[K+].[CH2:3]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([C:39]([O:41]C)=[O:40])=[C:11]([CH2:26][N:27]3[CH2:32][CH2:31][CH:30]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH2:29][CH2:28]3)[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=3)=[N:13]2)=[CH:8][C:7]=1[S:43]([CH3:46])(=[O:45])=[O:44])[CH3:4].[K]>CO.O>[CH2:3]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([C:39]([OH:41])=[O:40])=[C:11]([CH2:26][N:27]3[CH2:28][CH2:29][CH:30]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH2:31][CH2:32]3)[C:12]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:23])[F:24])[CH:17]=3)=[N:13]2)=[CH:8][C:7]=1[S:43]([CH3:46])(=[O:45])=[O:44])[CH3:4]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 5462222PotassiumHCID 67417923Methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 711829497-(Ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 106.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Potassium hydroxide (1.36 g, 2.42 mmol) was added to a solution of methyl 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.54 g, 2.423 mmol) in methanol (60 mL) and water (20 mL). The reaction mixture was heated to reflux overnight. The mixture was cooled to room temperature, diluted with water, and concentrated in vacuo to remove methanol. The solid precipitate was collected by filtration, washed with cold water, and dried to afford 7-(ethyloxy)-6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1.6 g, >99% yield) as the potassium salt. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.92 (d, J=7.53 Hz, 1H), 7.79 (d, J=7.78 Hz, 1H), 7.68 (t, J=7.78 Hz, 1H), 7.52 (s, 1H), 4.34 (q, J=6.94 Hz, 2H), 3.49-3.55 (m, 4H), 3.44 (s, 2H), 3.17 (s, 3H), 2.53 (br. s., 2H), 2.31-2.38 (m, 4H), 1.93-2.02 (m, 1H), 1.85 (t, J=11.29 Hz, 2H), 1.52 (d, J=11.04 Hz, 2H), 1.46 (t, J=7.03 Hz, 3H), 0.94-1.07 (m, 2H); MS (m/z) 622.2 (M+H+).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated in vacuo
  4. customto remove methanol
  5. filtrationThe solid precipitate was collected by filtration
  6. washwashed with cold water
  7. customdried

Sources & evidence

ORD record
ord-2b62a5220d4043d3a993d505d348954d
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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