Sodium Hydroxide → 2-{5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid

HRID 889752Notes

Reaction equation

HRID 889752 reaction equation
C([O:3][C:4](=[O:44])[CH:5]([C:10]1[CH:11]=[C:12]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([F:33])[CH:24]=3)[CH2:18][CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[Na+]>CO>[F:33][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:26]=1)[CH2:22][N:19]1[CH2:18][CH2:17][CH:16]([C:14]2[CH:15]=[C:10]([CH:5]([CH2:6][CH:7]([CH3:9])[CH3:8])[C:4]([OH:44])=[O:3])[CH:11]=[C:12]([C:34]3[CH:35]=[CH:36][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:39]=3)[CH:13]=2)[CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 576660322-{5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester

Product 1

HCID 252669202-{5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of a mixture of 2-{5-[1-(3-fluoro-5-trifluoromethyl-benzyl)-piperidin-4-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester and methyl ester (38 mg, 0.06 mmol) in MeOH (1 mL) was added 3N NaOH (0.750 mL) and heated to 60° C. for 2 h. The reaction was concentrated in vacuo to remove MeOH. The thick liquid was acidified to pH=2 by 2N HCl. The resulting acidic solution was extracted with EtOAc. The organic fraction was dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by Gilson reverse phase column chromatography to obtain 2-{5-[1-(3-fluoro-5-trifluoromethyl-benzyl)-piperidin-4-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid. 1H-NMR (MeOD-d4): δ 0.84 (d, 6H), 1.41 (m, 1H), 1.57 (m, 1H), 1.88-1.93 (m, 3H), 2.09 (m, 2H), 2.92 (t, 1H), 3.14 (t, 1H), 3.52 (m, 2H), 3.65 (t, 1H), 4.40 (s, 2H), 7.21 (s, 1H), 7.36 (s, 1H), 7.42 (s, 1H), 7.56-7.69 (m, 7H); Calcd for C32H32F7NO2 (M+H) 596.59, Found 596.40

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customto remove MeOH
  3. extractionThe resulting acidic solution was extracted with EtOAc
  4. dry with materialThe organic fraction was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified by Gilson reverse phase column chromatography

Sources & evidence

ORD record
ord-c62b1b37d1b644a5b6082a6144ac5026
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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