Sodium Hydroxide → 3-(1H-Indol-4-yl)benzoic acid

HRID 982996Notes

Reaction equation

HRID 982996 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.[C:11]([C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1)([OH:13])=[O:12].[OH-].[Na+]>C(#N)C.CN(C=O)C.[Pd]>[NH:6]1[C:7]2[C:3](=[C:2]([C:18]3[CH:19]=[C:14]([CH:15]=[CH:16][CH:17]=3)[C:11]([OH:13])=[O:12])[CH:10]=[CH:9][CH:8]=2)[CH:4]=[CH:5]1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 6764944-BromoindoleHCID 27339573-Carboxyphenylboronic acid

Product 1

HCID 225619543-(1H-Indol-4-yl)benzoic acidYield 71.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 4-bromoindole (11.81 g, 60.26 mmol), and 3-carboxyphenylboronic acid (10.0 g, 60.6 mmol) in acetonitrile (100 mL) and DMF (100 mL) were added Palladium catalyst Pd(PPh3)4 (2.09 g, 1.81 mmol) and the freshly prepared sodium hydroxide solution (9.64 g, 241 mmol in 80 mL water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under argon at 110° C. oil bath for 4 hours. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, filtered through celite, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed with brine, dried over MgSO4, and concentrated. The crude product was purified by a silica gel column eluting with DCM: Hexanes: acetic acid (100:1:1) to provide 10.2 g (71%) of 3-(1H-indol-4-yl)-benzoic acid as a gray yellow 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. filtrationfiltered through celite
  6. additiondiluted with ethyl acetate
  7. customseparated from water layer
  8. washThe ethyl acetate solution was washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe crude product was purified by a silica gel column
  12. washeluting with DCM: Hexanes: acetic acid (100:1:1)

Sources & evidence

ORD record
ord-1c50cfcec8fa4f1b86a97bbfcf2910e6
Source dataset
uspto-grants-2005_03
Patent number
US06861418B2

Reaction notes

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