Potassium Hydroxide → 4-Methyl-2-{5-[1-(4-pyrrol-1-yl-benzyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-pentanoic acid

HRID 889724Notes

Reaction equation

HRID 889724 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][CH2:19][N:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH:33]=[CH:32][CH:31]=[CH:30]4)=[CH:25][CH:24]=3)[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[K+]>CCO>[CH3:8][CH:7]([CH3:9])[CH2:6][CH:5]([C:10]1[CH:11]=[C:12]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:36][CH:35]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH:33]=[CH:32][CH:31]=[CH:30]4)=[CH:25][CH:24]=3)[CH2:17]2)[CH:15]=1)[C:4]([OH:44])=[O:3]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 576659934-Methyl-2-{5-[1-(4-pyrrol-1-yl-benzyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-pentanoic acid ethyl ester

Product 1

HCID 252707734-Methyl-2-{5-[1-(4-pyrrol-1-yl-benzyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-pentanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
78 °C

Procedure

To compound 44a, 4-Methyl-2-{5-[1-(4-pyrrol-1-yl-benzyl)-piperidin-3-yl]-4′-trifluoromethyl-biphenyl-3-yl}-pentanoic acid ethyl ester (56.2, 0.09 mmol) in EtOH (5 ml) was added 2M KOH (0.5 ml, 0.93 mmol). The reaction was heated to 78° C. for 1.5 hours, cooled to room temperature, and concentrated in vacuo. Purification via Gilson HPLC, salt exchange with 1N HCl (aqueous) gave the product as a white lyophilate, (32 mg, 56% ). 1H NMR (300 MHz, MeOD) δ ppm 0.89-0.97 (m, 6 H) 1.50 (dt, J=13.28, 6.74 Hz, 1 H) 1.67 (dt, J=13.47, 6.64 Hz, 1 H) 1.89-2.03 (m, 3 H) 2.05-2.15 (m, 2 H) 3.06-3.22 (m, 2 H) 3.52-3.63 (m, 2 H) 3.76 (t, J=7.72 Hz, 1 H) 4.39 (d, J=2.64 Hz, 2 H) 6.29-6.33 (m, 2 H) 7.23-7.26 (m, 2 H) 7.33 (s, 1 H) 7.54 (d, J=19.97 Hz, 2 H) 7.61 (s, 4 H) 7.78 (q, J=8.41 Hz, 4 H), Calcd for C35H37F3N2O2 (M+H) 574.68, Found 575.4.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customPurification via Gilson HPLC, salt exchange with 1N HCl (aqueous)
  4. customgave the product as a white lyophilate, (32 mg, 56% )

Sources & evidence

ORD record
ord-016b6d86201a486ea690087294016c57
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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