Sodium Hydroxide → HCID 22561761, compound

HRID 2068721Notes

Reaction equation

HRID 2068721 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][CH:23]=[C:22]([F:26])[C:21]=1[F:27].[OH-].[Na+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:26][C:22]1[C:21]([F:27])=[CH:20][CH:25]=[CH:24][C:23]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 27332601-Bromo-2,3-difluorobenzeneHCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 22561761HCID 22561761, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole 3b (1.22 g, 5 mmol) was dissolved in 20 mL of tetrahydrofuran under stirring under an argon atmosphere, and 1-bromo-2,3-difluoro-benzene (0.97 g, 5 mmol), tetrakis (triphenylphosphine) palladium (0.17 g, 0.15 mmol) and 7 mL of sodium hydroxide solution (2M) were then added to the solution. Upon completion of the addition, the reaction system was stirred at 75° C. in an oil bath overnight. The reaction was completed until TLC showed the disappearance of starting materials. The reaction mixture was naturally cooled down to room temperature and extracted with ethyl acetate (20 mL ×3). The combined organic extracts were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The resulting solid was purified by silica gel column chromatography to give the title compound 4-(2,3-difluoro-phenyl)-1H-indole 3c (800 mg, yield 70%) as a white solid.

Workup

  1. additionUpon completion of the addition
  2. stirringthe reaction system was stirred at 75° C. in an oil bath overnight
  3. extractionextracted with ethyl acetate (20 mL ×3)
  4. washThe combined organic extracts were washed with saturated brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customto remove the drying agent
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting solid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4518ecfbcaa14d49a81cedc67af8f380
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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