Potassium Acetate → Indole

HRID 425921Notes

Reaction equation

HRID 425921 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.B(OB([O-])[O-])([O-])[O-].CC([O-])=O.[K+].CCOC(C)=O.CCCCCC>CS(C)=O.[Pd]>[NH:6]1[C:7]2[C:3](=[CH:2][CH:10]=[CH:9][CH:8]=2)[CH:4]=[CH:5]1

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 6764944-BromoindoleHCID 21226206Ethyl acetate hexaneHCID 86587655Diborate

Product 1

HCID 798IndoleYield 21.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-bromoindole (9.80 g, 50 mmol), pinacole diborate (13.97 g, 55 mmol), and KOAc (14.72 g, 150 mmol) in DMSO (200 mL) was added palladium catalyst PdCl2(dppf)CH2Cl2 (1.22 g, 1.5 mmol). The system was degassed, and then charged with nitrogen for three times. The mixture was stirred at 80° C. oil bath under nitrogen for 22 hours. TLC showed the complete disappearance of the starting material 4-bromoindole. The mixture was cooled to room temperature, and then poured to water (1 L). The product was extracted with ethyl acetate for three times. The combined extracts were washed by brine for five times to remove DMSO solvent, and then dried over Na2SO4. During the washing step, the catalyst may precipitate out, which was removed by filtration. The ethyl acetate solution was filtered and condensed. The residue was purified on a silica gel column eluting with EtOAc-hexane (9:1). The first fraction provided the side product indole (1.25 g, 21% yield), Rf 0.55 (EtOAc-Hexane 5:1). The second fraction provided 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole as a white solid (8.01 g, 66%), Rf 0.46 (EtOAc-Hexane 5:1). 1H NMR (300 MHz, DMSO-d6): δ11.03 (bs, 1H, N—H)), 7.49 (d, J=7.7 Hz, 1H, H-5), 7.38 (dd, J=0.9 Hz, J=7.0 Hz, 1H, H-7), 7.38 (t, J=2.6 Hz, 1H, H-2), 7.06 (dd, J=7.7 Hz, J=7.0 Hz, 1H, H-6), 6.73 (bd, J 2.2 Hz; 1H, H-3), 1.32 (s, 12H, 4CH3); MS (m/e): 244 (M+H)+.

Workup

  1. customThe system was degassed
  2. additioncharged with nitrogen for three times
  3. temperatureThe mixture was cooled to room temperature
  4. additionpoured to water (1 L)
  5. extractionThe product was extracted with ethyl acetate for three times
  6. washThe combined extracts were washed by brine for five times
  7. customto remove DMSO solvent
  8. dry with materialdried over Na2SO4
  9. customDuring the washing step, the catalyst may precipitate out
  10. customwhich was removed by filtration
  11. filtrationThe ethyl acetate solution was filtered
  12. customcondensed
  13. customThe residue was purified on a silica gel column
  14. washeluting with EtOAc-hexane (9:1)

Sources & evidence

ORD record
ord-a05d082a27f0475aadd7e7ef1844e3a5
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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