Potassium Hydroxide → HCID 25268343, compound

HRID 889696Notes

Reaction equation

C([O:3][C:4](=[O:45])[CH:5]([C:10]1[CH:11]=[C:12]([C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][CH:18]([C:22]([F:25])([F:24])[F:23])[N:17]2[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[K+]>CCO>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:17]2[CH:18]([C:22]([F:24])([F:23])[F:25])[CH2:19][CH2:20][CH2:21][CH:16]2[C:14]2[CH:15]=[C:10]([CH:5]([CH2:6][CH:7]([CH3:8])[CH3:9])[C:4]([OH:45])=[O:3])[CH:11]=[C:12]([C:35]3[CH:40]=[CH:39][C:38]([C:41]([F:43])([F:44])[F:42])=[CH:37][CH:36]=3)[CH:13]=2)=[CH:32][CH:31]=1

Participants

Conditions

Temperature: 78 °C

Procedure

To 2-{5-[1-(4-Methoxy-benzyl)-6-trifluoromethyl-piperidin-2-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester, compound 7c (21.3 mg, 0.034 mmol) in EtOH (2 mL) was added 2M KOH (67 μl, 0.134 mmol). The reaction was heated to 78° C. for 5 hours, cooled to room temperature, and concentrated in vacuo. Purification via Gilson HPLC, followed by salt exchange with aqueous 1N HCl and subsequent lyophilization, gave the title compound as a white solid. (13 mg, 61%) 1H NMR (300 MHz, MeOD) δ ppm 0.89-0.99 (m, 6 H) 1.53 (dd, J=13.38, 6.59 Hz, 1 H) 1.68 (ddd, J=13.75, 7.16, 6.97 Hz, 1 H) 1.74-1.89 (m, 4 H) 1.92-2.07 (m, 3 H) 3.50-3.58 (m, 1H) 3.68 (s, 3 H) 3.67-3.82 (m, 4 H) 6.70 (d, J=8.67 Hz, 2 H) 7.01 (d, J=7.16 Hz, 2 H) 7.41-7.54 (m, 3 H) 7.68-7.77 (m, 4 H) Calcd for C33H35F6NO3 (M+H) 607.63, Found 608.4.

Workup

temperaturecooled to room temperature
concentrationconcentrated in vacuo
customPurification via Gilson HPLC

Sources & evidence

ORD record: ord-03aab15c1f3743928b2a3b566be2ff78
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252935B2

Reaction notes

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