Acetic Acid → 6-Bromoindole

HRID 1371846Notes

Reaction equation

HRID 1371846 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([N+:9]([O-])=O)[CH:3]=1.[CH3:12]N(C)C=O.N1CCCC1.C(O)(=O)C>CCOCC.[Zn]>[Br:1][C:2]1[CH:3]=[C:4]2[C:5]([CH:8]=[CH:12][NH:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 31268PyrrolidineHCID 1235464-Bromo-2-nitrotoluene

Product 1

HCID 6764936-Bromoindole

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
110 °C

Procedure

Combine 4-bromo-2-nitrotoluene (5.0 g, 23.1 mmol), dimethylformamide (50 ml), DMF-dimethylacetal (9.0 ml, 69.4 mmol), and pyrrolidine (2.0 ml, 23.1 mmol). Heat to 110° C. After 3 hours, cool to room temperature, dilute with ether, and wash with water. Combine the organic layers, and concentrate to give a residue. Combine the residue and 80% aq. acetic acid (120 ml) and heat at 75° C. Add zinc dust (13.1 g, 200.5 mmol) portionwise. Heat to 85° C. After 2 hours, cool and filter. Dilute the filtrate with ether, wash with water dry (Na2SO4), and concentrate to give a residue. Chromatograph the residue eluting with 9:1 hexane:EtOAc to give the title compound.

Workup

  1. temperaturecool to room temperature
  2. washwash with water
  3. concentrationconcentrate
  4. customto give a residue
  5. temperatureheat at 75° C
  6. temperatureHeat to 85° C
  7. waitAfter 2 hours
  8. temperaturecool
  9. filtrationfilter
  10. additionDilute the filtrate with ether
  11. washwash with water
  12. dry with materialdry (Na2SO4)
  13. concentrationconcentrate
  14. customto give a residue
  15. washChromatograph the residue eluting with 9:1 hexane

Sources & evidence

ORD record
ord-30817fdd4f02417799e847c9a86947a5
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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