Sodium Hydroxide → HCID 22561865, compound

HRID 982991Notes

Reaction equation

HRID 982991 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]([CH2:26][C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=1.[OH-].[Na+]>C1COCC1.[Pd].C(OCC)(=O)C>[NH:13]1[C:14]2[C:10](=[C:9]([C:20]3[CH:21]=[C:22]([CH2:26][C:27]([OH:29])=[O:28])[CH:23]=[CH:24][CH:25]=3)[CH:17]=[CH:16][CH:15]=2)[CH:11]=[CH:12]1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 74653(3-Bromophenyl)acetic acidHCID 113224711H-Indole-4-boronic acid, pinacol ester

Product 1

HCID 22561865HCID 22561865, compoundYield 84.3%

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 (15.52 g, 63.72 mmol), and 3-bromo-phenylacetic acid (13.78 g, 63.72 mmol) in THF (192 mL) were added Palladium catalyst Pd(PPh3)4 (2.21 g, 1.9 mmol) and the freshly prepared sodium hydroxide solution (7.65 g in 90 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 in a 70° C. oil bath for over the weekend. 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 water layer was acidified with dil. HCl solution to pH 4-5 and extracted with ethyl acetate. The ethyl acetate solution was washed with water, brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified on a silica gel column to give 13.5 g (84%) of [3-(1H-indol-4-yl)-phenyl]-acetic acid.

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. extractionextracted with ethyl acetate
  7. washThe ethyl acetate solution was washed with water, brine
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtration
  10. customthe solvents were evaporated
  11. customthe crude product was purified on a silica gel column

Sources & evidence

ORD record
ord-503f0af867994da0874dc6d74a2edfad
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Reaction notes

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