Sodium Azide → Methyl 7-fluoro-6-(2-fluorophenylamino)-3-methylbenzo[c]isoxazole-5-carboxylate

HRID 1161797Notes

Reaction equation

HRID 1161797 reaction equation
[C:1]([C:4]1[C:5](F)=[C:6]([F:22])[C:7]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])(=[O:3])[CH3:2].[N-:24]=[N+]=[N-].[Na+]>CC(C)=O.O>[F:22][C:6]1[C:5]2=[N:24][O:3][C:1]([CH3:2])=[C:4]2[CH:13]=[C:8]([C:9]([O:11][CH3:12])=[O:10])[C:7]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21]

Participants

5

Reactant 2

HCID 33557Sodium AzideHCID 59519431Methyl 5-acetyl-2-(2-fluorophenylamino)-3,4-difluorobenzoate

Product 1

HCID 59519479Methyl 7-fluoro-6-(2-fluorophenylamino)-3-methylbenzo[c]isoxazole-5-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent2×

Conditions

Temperature
65 °C

Procedure

To a solution of methyl 5-acetyl-3,4-difluoro-2-(2-fluorophenylamino)benzoate (example 3, step D) (1.50 g, 4.64 mmol) in a mixture of acetone (36 ml) and H2O (12 ml) was added NaN3 (452 mg, 6.96 mmol). The reaction was heated at 65° C. for 16 h and cooled to room temperature. Acetone was concentrated and the resulting mixture was extracted with EtOAc (2×50 ml). The combined organic solution was washed with brine (50 ml), dried over MgSO4 and concentrated to give a yellow solid. To the solid was added H2O (24 ml) and the reaction was heated at reflux for 3 h. The reaction was cooled to room temperature, filtered, and washed with H2O. The resulting solid was dried under high vacuum with P2O5 at 65° C. for 24 h to give 1.31 g (89%) of methyl 7-fluoro-6-(2-fluorophenylamino)-3-methylbenzo[c]isoxazole-5-carboxylate as a yellow solid.

Workup

  1. temperaturecooled to room temperature
  2. concentrationAcetone was concentrated
  3. extractionthe resulting mixture was extracted with EtOAc (2×50 ml)
  4. washThe combined organic solution was washed with brine (50 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give a yellow solid
  8. temperaturethe reaction was heated
  9. temperatureat reflux for 3 h
  10. temperatureThe reaction was cooled to room temperature
  11. filtrationfiltered
  12. washwashed with H2O
  13. dry with materialThe resulting solid was dried under high vacuum with P2O5 at 65° C. for 24 h

Sources & evidence

ORD record
ord-b37c440abe2f4301a5f2ad73e1d3bcec
Source dataset
uspto-grants-2010_10
Patent number
US07820664B2

Reaction notes

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