Sodium Hydroxide → HCID 25269422, compound

HRID 889766Notes

Reaction equation

HRID 889766 reaction equation
C[O:2][C:3](=[O:39])[C@@H:4]([C:9]1[CH:10]=[C:11]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=2)[CH:12]=[C:13]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:14]=1)[CH2:5][CH:6]([CH3:8])[CH3:7].[OH-].[Na+]>CO>[CH3:7][CH:6]([CH3:8])[CH2:5][C@H:4]([C:9]1[CH:10]=[C:11]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:37])([F:36])[F:38])=[CH:31][CH:30]=2)[CH:12]=[C:13]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]2[CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:14]=1)[C:3]([OH:39])=[O:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 57666050HCID 57666050, compound

Product 1

HCID 25269422HCID 25269422, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (R)-4-methyl-2-[5-(2-phenethyl-piperidin-1-yl)-4′-trifluoromethyl-biphenyl-3-yl]-pentanoic acid methyl ester (14 mg, 0.03 mmol) in MeOH (2 mL) was added 1N NaOH (0.100 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 (R)-4-methyl-2-[5-(2-phenethyl-piperidin-1-yl)-4′-trifluoromethyl-biphenyl-3-yl]-pentanoic acid. 1H-NMR (MeOD-d4): δ 0.84 (m, 6H), 1.40 (m, 1H), 1.60-1.76 (m, 5H), 1.93 (m, 4H), 2.28-2.41 (m, 2H), 2.59 (m, 1H), 3.56-3.73 (m, 3H), 3.78 (q, 1H), 6.85 (s, 1H), 6.87 (s, 1H), 6.98 (m, 1H), 7.04 (m, 2H), 7.47-7.57 (m, 2H), 7.71 (s, 5H); Calcd for C32H36F3NO2 (M+H) 524.63, Found 524.3

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-b13e860f79ea47e68c51f744b16d76f3
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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