Ammonium Acetate → 4-Fluoro-5-methoxy-2-methyl-1H-indole

HRID 454221Notes

Reaction equation

HRID 454221 reaction equation
[C:1]([CH2:4][C:5]1[C:6]([F:16])=[C:7]([O:14][CH3:15])[CH:8]=[CH:9][C:10]=1[N+:11]([O-])=O)(=O)[CH3:2].C([O-])(=O)C.[NH4+]>CC(C)=O.[Cl-].[Cl-].[Cl-].[Ti+3]>[F:16][C:6]1[C:7]([O:14][CH3:15])=[CH:8][CH:9]=[C:10]2[C:5]=1[CH:4]=[C:1]([CH3:2])[NH:11]2

Participants

5

Reactant 2

HCID 517165Ammonium AcetateHCID 220307431-(2-Fluoro-3-methoxy-6-nitrophenyl)propan-2-one

Product 1

HCID 220307284-Fluoro-5-methoxy-2-methyl-1H-indoleYield 91%

Reagents, catalysts & solvents 2

HCID 10313229titanium(III) trichlorideCatalystHCID 180AcetoneSolvent

Procedure

To a solution of 3-acetylmethyl-2-fluoro-1-methoxy-4-nitrobenzene (11.36 g, 50 mmol) in acetone (200 ml) was added 4M aqueous ammonium acetate (700 ml) followed by a solution of titanium trichloride (15% in water, 340 ml) dropwise. The mixture was stirred for 10 minutes at ambient temperature and the mixture was extracted with ether. The organic layer was washed with 0.5N aqueous sodium hydroxide followed by water, brine, dried (MgSO4) and the volatiles were removed under vacuum. The residue was purified by column chromatography eluting with methylene chloride to give 4-fluoro-5-methoxy-2-methylindole (8.15 g, 90%).

Workup

  1. extractionthe mixture was extracted with ether
  2. washThe organic layer was washed with 0.5N aqueous sodium hydroxide
  3. dry with materialdried (MgSO4)
  4. customthe volatiles were removed under vacuum
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride

Sources & evidence

ORD record
ord-97986bb19a6e403b8c830abc576cc4b6
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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