p-Bromochlorobenzene → 4-(4-Chloro-phenyl)-1H-indole

HRID 982978Notes

Reaction equation

HRID 982978 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:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 7806p-BromochlorobenzeneHCID 14798Sodium HydroxideHCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 225617474-(4-Chloro-phenyl)-1H-indoleYield 89%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (3, 2.43 g, 10 mmol), and 4-bromochlorobenzene (2.87 g, 15 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 15 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 2.02 g (89%) of the product 4-(4-chloro-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-9bd719bd920742fe9ad0cf4bd000bd15
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Reaction notes

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