Diethyl Ether → 5-Bromo-1-(4-fluoro-phenyl)-3-methyl-1H-indole

HRID 1633685Notes

Reaction equation

HRID 1633685 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:11].Br[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1.[OH-].[K+].CCOCC>[Cu]I.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH:6]=[C:5]2[CH3:11]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 99931-Bromo-4-fluorobenzeneHCID 14797Potassium HydroxideHCID 2547075-Bromo-3-methyl-1H-indole

Product 1

HCID 186794425-Bromo-1-(4-fluoro-phenyl)-3-methyl-1H-indoleYield 12.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Procedure

To 4.2 g (20 mmol) 5-Bromo-3-methyl-1H-indole [prepared according to Noland, Wayland E.; Reich, Charles. Synthesis and reactions of 5-bromoskatole and 5-bromo-1,3-dimethylindole. J. Org. Chem. (1967), 32(3), 828-32.] in 22 ml (0.2 mol) 1-bromo-4-fluorobenzene were added 5.6 g (0.1 mol) powdered potassium hydroxide and 1.14 g (60 mmol) CuI as powder. The suspension was heated to reflux for 0.5 h. At RT, ether and water were added, the phases were separated and the aqueous phase was extracted with ether. The combined organic phases were washed with water and dried over Na2SO4. Column chromatography on silica gel with hexane yielded 750 mg 5-Bromo-1-(4-fluoro-phenyl)-3-methyl-1H-indole as colorless solid, mp 97-98° C., MS: 303(M, 1Br).

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 0.5 h
  3. customthe phases were separated
  4. extractionthe aqueous phase was extracted with ether
  5. washThe combined organic phases were washed with water
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-0e25df5824b04b6f8569244c4f6ae450
Source dataset
uspto-grants-2003_01
Patent number
US06503907B2

Reaction notes

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