Sulfuric Acid → Methyl 5-acetyl-2-(2-fluorophenylamino)-3,4-difluorobenzoate

HRID 1161792Notes

Reaction equation

HRID 1161792 reaction equation
[F:1][C:2]1[C:3]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])=[C:4]([CH:9]=[C:10]([C:13]#[C:14][Si](C)(C)C)[C:11]=1[F:12])[C:5]([O:7][CH3:8])=[O:6].[OH:27]S(O)(=O)=O>CC(C)=O>[C:13]([C:10]1[C:11]([F:12])=[C:2]([F:1])[C:3]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])=[C:4]([CH:9]=1)[C:5]([O:7][CH3:8])=[O:6])(=[O:27])[CH3:14]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 59519400Methyl 2-(2-fluorophenylamino)-3,4-difluoro-5-((trimethylsilyl)ethynyl)benzoate

Product 1

HCID 59519431Methyl 5-acetyl-2-(2-fluorophenylamino)-3,4-difluorobenzoateYield 81%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of methyl 3,4-difluoro-2-(2-fluorophenylamino)-5-((trimethylsilyl)ethynyl)benzoate (1.20 g, 3.18 mmol) in 85% aqueous acetone (40 ml) were added HgSO4 (943 mg, 3.18 mmol) and H2SO4 (0.33 ml, 6.36 mmol). The reaction was heated at reflux for 24 h. The mixture was cooled to room temperature, concentrated, and diluted with EtOAc (100 ml). The organic solution was washed with H2O (50 ml), dried over Na2SO4 and concentrated. Silica gel chromatography (EtOAc:Hexanes=10:90) yielded 832 mg (81%) of methyl 5-acetyl-3,4-difluoro-2-(2-fluorophenylamino)benzoate as a white solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. concentrationconcentrated
  4. additiondiluted with EtOAc (100 ml)
  5. washThe organic solution was washed with H2O (50 ml)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-89f8c0dac5fa4c97bf6f27a6be40cdb8
Source dataset
uspto-grants-2010_10
Patent number
US07820664B2

Reaction notes

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