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

HRID 1975970Notes

Reaction equation

HRID 1975970 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 tie 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 and tie reaction mixture
  2. concentrationwas concentrated
  3. customchromatographed on silica gel
  4. washto elute the product (0.8 g) as a white foam

Sources & evidence

ORD record
ord-1db14da3d64f4eec95491ec58c88a2e5
Source dataset
uspto-grants-2001_05
Patent number
US06225308B1

Reaction notes

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