Water → 3-{[4-(3,3-Difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245249Notes

Reaction equation

HRID 245249 reaction equation
[F:1][C:2]1([F:42])[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[C:15]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=4)=[N:16][C:17]4[C:22]([C:23]=3[C:24]([O:26]C)=[O:25])=[CH:21][C:20]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:19][CH:18]=4)[CH2:9][CH2:8]2)[CH2:3]1.O.[OH-].[K+]>CO>[F:42][C:2]1([F:1])[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[C:15]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[CH:33]=4)=[N:16][C:17]4[C:22]([C:23]=3[C:24]([OH:26])=[O:25])=[CH:21][C:20]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:19][CH:18]=4)[CH2:9][CH2:8]2)[CH2:3]1

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 67384024Methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 673832513-{[4-(3,3-Difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 75.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (0.970 g, 1.586 mmol) in methanol (15.86 mL) was added water (5.29 mL) and potassium hydroxide (0.445 g, 7.93 mmol). The mixture was heated to 65° C. for 15 h. The mixture was cooled to room temperature and concentrated. The residue was acidified to pH 4-5 with 2N HCl. The resulting precipitate was collected by filtration, washed with water (2×1 mL), and dried in the vacuum oven (35° C.) overnight to provide 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.718 g, 72% yield) as a yellow solid. MS (m/z) 598.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with water (2×1 mL)
  5. customdried in the vacuum oven (35° C.) overnight

Sources & evidence

ORD record
ord-4761529306fe4a28a8a1ae48791160f5
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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