Sulfuric Acid → 6-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester

HRID 1723682Notes

Reaction equation

HRID 1723682 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C:4]1[C:9]([C:10]#[C:11][Si](C)(C)C)=[CH:8][C:7]([F:16])=[C:6]([F:17])[C:5]=1[NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25].[OH:27]S(O)(=O)=O>CC(C)=O.O>[CH3:1][O:2][C:3](=[O:26])[C:4]1[C:9]([C:10](=[O:27])[CH3:11])=[CH:8][C:7]([F:16])=[C:6]([F:17])[C:5]=1[NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 865985932-(2-Chlorophenylamino)-3,4-difluoro-6-trimethylsilanylethynylbenzoic acid methyl ester

Product 1

HCID 865985946-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A mixture of 2-(2-chlorophenylamino)-3,4-difluoro-6-trimethylsilanylethynylbenzoic acid methyl ester (1.00 g, 2.54 mmol), HgSO4 (761 mg, 2.54 mmol), and concentrated H2SO4 (0.27 mL) in acetone-water (22 mL/4 mL) was refluxed for 3 hours. The reaction mixture was concentrated in vacuo, diluted with EtOAc-THF, and washed with water and brine. The organic layer was dried over MgSO4, filtered, and concentrated to give the crude material that was purified by silica gel flash column chromatography (8% EtOAc in hexanes) to afford the desired product (496 mg, 58%).

Workup

  1. temperaturewas refluxed for 3 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiondiluted with EtOAc-THF
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude material that
  9. customwas purified by silica gel flash column chromatography (8% EtOAc in hexanes)

Sources & evidence

ORD record
ord-75ed1b09b8014952b1cd82a92cb8c721
Source dataset
uspto-grants-2009_02
Patent number
US07485643B2

Reaction notes

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