1,3-Cyclohexadiene → 2-(4-Hydroxy-phenyl)-3-methyl-1-{4-[3-(piperidin-1-yl)-propoxy]-benzyl}-1H-indol-5-ol

HRID 269866Notes

Reaction equation

HRID 269866 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:21][CH:20]=1)[C:13]([C:35]1[CH:40]=[CH:39][C:38]([O:41]CC3C=CC=CC=3)=[CH:37][CH:36]=1)=[C:12]2[CH3:49])C1C=CC=CC=1.C1CCC=CC=1>O1CCCC1.C(O)C.[Pd]>[OH:41][C:38]1[CH:39]=[CH:40][C:35]([C:13]2[N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)=[CH:21][CH:20]=3)[C:15]3[C:11]([C:12]=2[CH3:49])=[CH:10][C:9]([OH:8])=[CH:17][CH:16]=3)=[CH:36][CH:37]=1

Participants

6

Reactant 2

HCID 116051,3-CyclohexadieneHCID 102116765-Benzyloxy-2-(4-benzyloxy-phenyl)-1-(4-(3-piperidin-1-yl-propoxy)-benzyl]-3-methyl-1H-indole

Product 1

HCID 102054602-(4-Hydroxy-phenyl)-3-methyl-1-{4-[3-(piperidin-1-yl)-propoxy]-benzyl}-1H-indol-5-ol

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-3-methyl-1H-indole No. 165 (2.35 g) in tetrahydrofuran (25 mL) and ethanol (25 mL) was added to 2.3 g of 10% palladium on carbon. Cyclohexadiene (10 mL) was added and the reaction allowed to stir at room temperature for 18 hours. The catalyst was filtered through celite and the reaction mixture was concentrated and chromatographed on silica gel using dichloromethane/methanol (4:1) to elute the product (0.8 g) as a white foam: Mp=125-130° C.; 1H NMR 9.68 (s, 1 H), 8.70 (s, 1 H), 7.15 (d, 2 H, J=8.6 Hz), 7.05 (d, 1 H, J=8.8 Hz), 6.85 (d, 2 H, J=8.6 Hz), 6.80 (d, 1 H, J=2.4 Hz), 6.74 (d, 4 H, J=2.6 Hz), 6.57 (dd, 1 H, J=8.6, 2.2 Hz), 5.09 (s, 2 H), 3.88 (t, 2 H, J=6.4 Hz), 3.60-3.15 (m, 2 H), 2.62-2.38 (m, 4 H), 2.09 (s, 3 H), 1.92-1.78 (m, 2 H), 1.55-1.43 (m, 4 H), 1.42-1.30 (m, 2 H); IR (KBr) 3400 (br), 2900, 1620, 1515 cm−1; MS eI m/z 470.

Workup

  1. filtrationThe catalyst was filtered through celite
  2. concentrationthe reaction mixture was concentrated
  3. customchromatographed on silica gel
  4. washto elute the product (0.8 g) as a white foam

Sources & evidence

ORD record
ord-ee847d2516334ff0be8e5b802682bc18
Source dataset
uspto-grants-2008_11
Patent number
US07449455B2

Reaction notes

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