Sodium Hydroxide → 4-(4-Methoxyphenyl)-1H-indole

HRID 1839579Notes

Reaction equation

HRID 1839579 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[CH:4]=[CH:5][NH:6]3)=[CH:15][CH:14]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 201262(4-Methoxyphenyl)boronic acidHCID 6764944-Bromoindole

Product 1

HCID 225619404-(4-Methoxyphenyl)-1H-indoleYield 83%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-bromoindole (1.96 g, 10 mmol), and 4-methoxyphenylboronic acid (1.52 g, 10 mmol) in THF (34 mL)) were added Palladium catalyst Pd(PPh3)4 (347 mg, 0.3 mmol) and the freshly prepared sodium hydroxide solution (1.20 g, 30 mmol in 14 mL water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen at 70° C. oil bath for 16 hours. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed by brine, dried over Na2SO4, and concentrated. The crude product was purified by a silica gel column eluting with hexanes—EtOAc (9:1) to provide 1.85 g (83%) of the product 4-(4-Methoxy-phenyl)-1H-indole as a white solid.

Workup

  1. customThe system was degassed
  2. additioncharged with nitrogen
  3. customthe completion of the coupling reaction
  4. temperatureThe mixture was cooled to room temperature
  5. customseparated from water layer
  6. washThe ethyl acetate solution was washed by brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude product was purified by a silica gel column
  10. washeluting with hexanes—EtOAc (9:1)

Sources & evidence

ORD record
ord-f9d07616002a40e2a405cd0e347ad146
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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