Sodium Carbonate → 4-(2,6-difluoro-phenyl)-1H-indole

HRID 982995Notes

Reaction equation

HRID 982995 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[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=1[F:27].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.[Pd].C(OCC)(=O)C>[F:26][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]([F:27])[C:20]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 1235571-Bromo-2,6-difluorobenzeneHCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 225617024-(2,6-difluoro-phenyl)-1H-indoleYield 91.5%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (11.34 g, 46.6 mmol), and 1-bromo-2,6-difluorobenzene (9 g, 46.6 mmol) in 1,2-dimethoxyethane (204 mL) were added Palladium catalyst Pd(PPh3)4 (1.62 g, 1.4 mmol) and the freshly prepared sodium carbonate solution (15.19 g in 66 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 110° 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 9.77 g (91%) of 4-(2,6-difluoro-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-aeff157433714a52bad26c59625b8a2f
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Reaction notes

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