Sodium Hydroxide → 4-(3,4-Dimethoxyphenyl)-1H-indole

HRID 1839595Notes

Reaction equation

HRID 1839595 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)O1.Br[C:20]1[CH:21]=[C:22]([O:28][CH3:29])[C:23]([O:26][CH3:27])=[CH:24][CH:25]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[CH3:27][O:26][C:23]1[CH:24]=[C:25]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)[CH:20]=[CH:21][C:22]=1[O:28][CH3:29]

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 225616844-(3,4-Dimethoxyphenyl)-1H-indoleYield 72%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (10 g, 41.1 mmol), and 4-bromoveratrole (8.93 g, 41.1 mmol) in THF (140 mL) were added Palladium catalyst Pd(PPh3)4 (1.43 g, 1.23 mmol) and the freshly prepared sodium hydroxide solution (5.08 g in 58 mL of 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 80° C. oil bath for overnight. 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 with brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified by a silica gel column to give 7.47 g (72%) of 4-(3,4-dimethoxy-phenyl)-1H-indole.

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 with brine
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration
  9. customthe solvents were evaporated
  10. customthe crude product was purified by a silica gel column

Sources & evidence

ORD record
ord-a4efe9b137ec4e15b3f5c7f20674f1ff
Source dataset
uspto-grants-2004_01
Patent number
US06677368B2

Reaction notes

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