Sulfuric Acid → 5-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester

HRID 500566Notes

Reaction equation

HRID 500566 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C:4]1[CH:9]=[C:8]([C:10]#[C:11][Si](C)(C)C)[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[CH:9]=[C:8]([C:10](=[O:27])[CH3:11])[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 865967722-(2-Chlorophenylamino)-3,4-difluoro-5-trimethylsilanylethynylbenzoic acid methyl ester

Product 1

HCID 865967735-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl esterYield 73%

Reagents, catalysts & solvents 1

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

Procedure

A mixture of 2-(2-chlorophenylamino)-3,4-difluoro-5-trimethylsilanylethynylbenzoic acid methyl ester (7.11 g, 18.1 mmol), HgSO4 (5.43 g, 18.1 mmol), and conc. H2SO4 (1.92 mL, 36.1 mmol) in acetone-water (150 mL/25 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 in vacuo to give the crude material which was triturated with MeOH to afford the desired product (4.46 g, 73%).

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 in vacuo
  8. customto give the crude material which
  9. customwas triturated with MeOH

Sources & evidence

ORD record
ord-9d553e1f3bb74539a962ed6d2e6e8c0d
Source dataset
uspto-grants-2010_08
Patent number
US07772234B2

Reaction notes

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