Water → 6-Bromoindole

HRID 240830Notes

Reaction equation

HRID 240830 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]OC(OC)N(C)C.N1CCCC1.O>CN(C=O)C.[Zn].C(O)(=O)C>[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

8

Reactant 4

HCID 962WaterHCID 31268PyrrolidineHCID 78373Dimethylformamide dimethyl acetalHCID 1235464-Bromo-2-nitrotoluene

Product 1

HCID 6764936-BromoindoleYield 39.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture solution of 4-bromo-2-nitrotoluene (2.00 g, 9.26 mmol) and dimethylformamide-dimethylacetal (3.68 mL, 27.8 mmol) in DMF (20 mL), pyrrolidine (1.16 mL, 13.9 mmol) was added at room temperature. After stirring at 110° C. for an hour, the mixture was cooled to room temperature and then water was added. After extracting 3 times with ether, the collected organic layer was dried with anhydrous magnesium sulfate and the concentrated. The resulting residue was subjected to the next reaction without purification. After adding 80% acetic acid aqueous solution (60 mL), the mixture was heated to 85° C. While adding zinc powder (5.27 g, 80.6 mmol) in small amounts, the mixture was stirred at 85° C. for 2 hours. After cooling to room temperature and filtering, followed by addition of water, the filtrate was extracted with ethyl acetate. The collected organic layer was washed with brine and concentrated by drying with anhydrous magnesium sulfate. The residue was purified by chromatography (silica gel, EA:Hx=1:20). The target compound (710 mg) was obtained as violet solid.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. extractionAfter extracting 3 times with ether
  3. dry with materialthe collected organic layer was dried with anhydrous magnesium sulfate
  4. customThe resulting residue was subjected to the next reaction without purification
  5. temperaturethe mixture was heated to 85° C
  6. stirringthe mixture was stirred at 85° C. for 2 hours
  7. temperatureAfter cooling to room temperature
  8. filtrationfiltering
  9. additionfollowed by addition of water
  10. extractionthe filtrate was extracted with ethyl acetate
  11. washThe collected organic layer was washed with brine
  12. concentrationconcentrated
  13. dry with materialby drying with anhydrous magnesium sulfate
  14. customThe residue was purified by chromatography (silica gel, EA:Hx=1:20)

Sources & evidence

ORD record
ord-3721e4b0e5134698ad8cf70000861bbc
Source dataset
uspto-grants-2014_02
Patent number
US08648089B2

Reaction notes

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