Acetone → 6-(2-Chlorophenylamino)-7-fluoro-3-methyl-benzo[c]-isoxazole-5-carboxylic acid methyl ester

HRID 1788247Notes

Reaction equation

HRID 1788247 reaction equation
[N-:1]=[N+]=[N-].[Na+].[CH3:5][O:6][C:7](=[O:27])[C:8]1[CH:13]=[C:12]([C:14](=[O:16])[CH3:15])[C:11](F)=[C:10]([F:18])[C:9]=1[NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Cl:26].CC(C)=O>CCOC(C)=O.O>[CH3:5][O:6][C:7]([C:8]1[C:9]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[Cl:26])=[C:10]([F:18])[C:11]2=[N:1][O:16][C:14]([CH3:15])=[C:12]2[CH:13]=1)=[O:27]

Participants

6

Reactant 3

HCID 180AcetoneHCID 33557Sodium AzideHCID 865967735-Acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester

Product 1

HCID 688605096-(2-Chlorophenylamino)-7-fluoro-3-methyl-benzo[c]-isoxazole-5-carboxylic acid methyl esterYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Sodium azide (128 mg, 1.95 mmol) was added to a mixture of 5-acetyl-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester (6) (601 mg, 1.59 mmol) in 3:1 acetone:water (16 ml) and heated to reflux. After 16 hours, the reaction mixture was cooled to room temperature, and diluted with EtOAc and water. The organic layer was washed with water, dried (MgSO4) and concentrated. The resulting residue was diluted with water (8 mL) and heated to reflux. After 5 hours, the mixture was cooled to room temperature and diluted with EtOAc. The organic layer was washed with water, dried (MgSO4) and concentrated. Purification by flash column chromatography using the Biotage system (20% EtOAc in hexanes) provided the desired product (55) (410 mg, 77%).

Workup

  1. washThe organic layer was washed with water
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. additionThe resulting residue was diluted with water (8 mL)
  5. temperatureheated to reflux
  6. waitAfter 5 hours
  7. temperaturethe mixture was cooled to room temperature
  8. additiondiluted with EtOAc
  9. washThe organic layer was washed with water
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-db32bc23350740f1abb6cc7cce0f9309
Source dataset
uspto-grants-2009_03
Patent number
US07511058B2

Reaction notes

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