Potassium Hydroxide → 2-{5-[1-(1-Ethyl-propyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid

HRID 889711Notes

Reaction equation

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

Participants

Conditions

Temperature: 78 °C

Procedure

To a solution of compound 33c, 2-{5-[1-(1-Ethyl-propyl)-piperidin-3-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester (30.7 mg, 59.3 μmol) in EtOH (3 ml) was added 2M KOH (119 μl, 0.24 mmol). The reaction was heated to 78° C. for 2.5 hours, cooled to room temperature, and concentrated in vacuo. Purification via Gilson HPLC, followed by salt exchange with aqueous 1N HCl, gave the product as a white solid. (10.2 mg, 35% ) 1H NMR (300 MHz, MeOD) δ ppm 0.85 (d, J=6.78 Hz, 6 H) 0.99 (td, J=7.35, 3.77 Hz, 6 H) 1.35-1.49 (m, 1 H) 1.56-1.70 (m, 3 H) 1.79-1.93 (m, 4 H) 1.94-2.08 (m, 4H) 2.99 (dd, J=7.91, 4.14 Hz, 1 H) 3.05-3.15 (m, 2 H) 3.41 (s, 2 H) 3.68 (t, J=7.72 Hz, 1 H) 7.27 (s, 1 H) 7.47 (d, J=9.80 Hz, 2 H) 7.64-7.75 (m, 4 H) Calcd for C29H38F3NO2 (M+H) 489.61, Found 490.4.

Workup

temperaturecooled to room temperature
concentrationconcentrated in vacuo
customPurification via Gilson HPLC

Sources & evidence

ORD record: ord-19138cbdf0064b9a876d24e0d4b3a263
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252935B2

Reaction notes

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