Sodium Hydroxide → HCID 22561870, compound

HRID 982986Notes

Reaction equation

HRID 982986 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.[F:11][C:12]([F:24])([F:23])[O:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[F:11][C:12]([F:23])([F:24])[O:13][C:14]1[CH:15]=[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:17]=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 6764944-BromoindoleHCID 27343864-(Trifluoromethoxy)phenylboronic acid

Product 1

HCID 22561870HCID 22561870, compoundYield 87.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 4-bromoindole (4.50 g, 22.95 mmol), and 4-trifluoromethoxyphenylboronic acid (4.73 g, 22.95 mmol) in THF (78 mL)) were added Palladium catalyst Pd(PPh3)4 (795.6 mg, 0.69 mmol) and the freshly prepared sodium hydroxide solution (2.75 g, 68.9 mmol in 32 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 75° 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 5.56 g (78%) of the product 4-(4-trifluoromethoxy-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 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-b1c4e548f7564d7e8377c88a4420ad2e
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Reaction notes

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