Ethylene Glycol → 2-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethanol

HRID 717516Notes

Reaction equation

HRID 717516 reaction equation
[CH2:1]([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](I)=[CH:21][CH:20]=1)[C:13]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:28][CH:27]=1)=[C:12]2[CH3:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:41]([OH:44])[CH2:42][OH:43].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)CCC.[Cu](I)I>[CH2:1]([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:43][CH2:42][CH2:41][OH:44])=[CH:21][CH:20]=1)[C:13]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[CH:28][CH:27]=1)=[C:12]2[CH3:40])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 120740765-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indole

Product 1

HCID 121331372-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethanolYield 61.5%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8008ButyronitrileSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indole (1.01 g, 1.58 mmol), ethylene glycol (0.44 mL, 7.89 mmol), copper iodide (32 mg, 0.17 mmol), 1,10-phenanthroline (60 mg, 0.33 mmol), and potassium carbonate (436 mg, 3.15 mmol) in butyronitrile (3 mL) was degassed with three vacuum/N2 cycles. The reaction was heated at 125° C. for 26 hrs and upon completion, allowed to cool to room temperature. It was then diluted with water. The aqueous layer was extracted three times with ethyl acetate. The combined ethyl acetate extracts were washed with water (40 mL) and brine (40 mL), dried (MgSO4), filtered, concentrated and purified by silica gel chromatography (0%-40% ethyl acetate in hexanes) to give 554 mg of 2-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethanol as a pale yellow foam. 1H NMR (400 MHz, DMSO-d6): δ 7.48 (d, 4H), 7.45-7.37 (m, 4H), 7.37-7.32 (m, 2H), 7.30 (d, 2H), 7.21 (d, 1H), 7.15-7.10 (m, 3H), 6.81 (dd, 1H), 6.74 (s, 4H), 5.20-5.10 (m, 6H), 4.81 (t, 1H), 3.87 (t, 2H), 3.64 (q, 2H), 2.16 (s, 3H). LCMS: 570.0 (M+H)+.

Workup

  1. customwas degassed with three vacuum/N2 cycles
  2. temperatureto cool to room temperature
  3. additionIt was then diluted with water
  4. extractionThe aqueous layer was extracted three times with ethyl acetate
  5. washThe combined ethyl acetate extracts were washed with water (40 mL) and brine (40 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (0%-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8b310ce676094eeb89fc4d2a7c35ef7b
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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