Potassium Hydroxide → HCID 25271115, compound

HRID 889730Notes

Reaction equation

HRID 889730 reaction equation
C([O:3][C:4](=[O:47])[CH:5]([C:10]1[CH:11]=[C:12]([C:37]2[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=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]([O:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)=[CH:25][CH:24]=3)[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[K+]>CCO>[F:36][C:33]1[CH:34]=[CH:35][C:30]([O:29][C:26]2[CH:25]=[CH:24][C:23]([CH2:22][N:18]3[CH2:19][CH2:20][CH2:21][CH:16]([C:14]4[CH:15]=[C:10]([CH:5]([CH2:6][CH:7]([CH3:8])[CH3:9])[C:4]([OH:47])=[O:3])[CH:11]=[C:12]([C:37]5[CH:42]=[CH:41][C:40]([C:43]([F:45])([F:44])[F:46])=[CH:39][CH:38]=5)[CH:13]=4)[CH2:17]3)=[CH:28][CH:27]=2)=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 57665946HCID 57665946, compound

Product 1

HCID 25271115HCID 25271115, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
78 °C

Procedure

To compound 48a, 2-(5-{1-[4-(4-Fluoro-phenoxy)-benzyl]-piperidin-3-yl}-4′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid ethyl ester (52.3 mg, 0.08 mmol) in EtOH (5.0 ml) was added 2M KOH (0.40 ml, 0.8 mmol). The reaction was heated to 78° C. for 3 hour, 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, (41 mg, 76%). 1H NMR (400 MHz, MeOD) δ ppm 0.90-0.96 (m, 6 H) 1.51 (ddd, J=13.08, 6.72, 6.60 Hz, 1 H) 1.68 (dt, J=13.76, 6.94 Hz, 1 H) 1.88-1.93 (m, 2 H) 1.95-2.03 (m, 1 H) 2.11 (s, 2 H) 3.06 (d, J=2.93 Hz, 2 H) 3.22 (t, J=12.96 Hz, 1 H) 3.48-3.57 (m, 2 H) 3.77 (t, J=7.70 Hz, 1 H) 4.33 (s, 2 H) 7.00-7.10 (m, 5 H) 7.14 (d, J=1.96 Hz, 1 H) 7.24-7.34 (m, 2 H) 7.44-7.50 (m, 2 H) 7.58 (s, 1 H) 7.74-7.83 (m, 4 H), Calcd for C37H37F4NO3 (M+H) 619.69, Found 620.4.

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, (41 mg, 76%)

Sources & evidence

ORD record
ord-48afac089ce04894a2275c136b8b7563
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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