Quinoline → 4-bromo-5-methoxy-1H-indole

HRID 454285Notes

Reaction equation

HRID 454285 reaction equation
[Br:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5](C(O)=O)[NH:6]2.N1C2C(=CC=CC=2)C=CC=1>[Cr]([O-])([O-])=O.[Cu+2]>[Br:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2

Participants

4

Reactant 2

HCID 7047QuinolineHCID 133565154-Bromo-5-methoxy-1H-indole-2-carboxylic acid

Product 1

HCID 220305584-bromo-5-methoxy-1H-indoleYield 67%

Reagents, catalysts & solvents 1

HCID 178505374HCID 178505374, compoundCatalyst

Conditions

Temperature
245 °C

Procedure

4-Bromo-5-methoxyindole-2-carboxylic acid (1.25 g, 4.19 mmol), quinoline (15 ml) and copper chromite (313 mg) were mixed together. Nitrogen was gently bubbled through the mixture for 5 minutes, then the mixture heated quickly to 245° C. under an atmosphere of nitrogen. After 90 minutes the mixture was cooled to ambient temperature diluted with ethyl acetate (100 ml) and washed with 2M aqueous hydrochloric acid (60 ml). The ethyl acetate layer was filtered, the filtrate dried (MgSO4) and the solvent evaporated. The residue was purified by silica column chromatography eluting with dichloromethane/hexane (1/1) to give 4-bromo-5-methoxyindole (635 mg, 60%).

Workup

  1. customNitrogen was gently bubbled through the mixture for 5 minutes
  2. temperatureAfter 90 minutes the mixture was cooled to ambient temperature
  3. additiondiluted with ethyl acetate (100 ml)
  4. washwashed with 2M aqueous hydrochloric acid (60 ml)
  5. filtrationThe ethyl acetate layer was filtered
  6. dry with materialthe filtrate dried (MgSO4)
  7. customthe solvent evaporated
  8. customThe residue was purified by silica column chromatography
  9. washeluting with dichloromethane/hexane (1/1)

Sources & evidence

ORD record
ord-0fdf936fdda14e459420b187dfba4f1b
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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