Hydroxylamine → 5-Bromo-3-isopropylbenzo[d]isoxazole

HRID 1711790Notes

Reaction equation

HRID 1711790 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:13])=[C:6]([C:8](=O)[CH:9]([CH3:11])[CH3:10])[CH:7]=1.[NH2:14]O.C(OC(=O)C)(=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CCO.CC(O)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:13][N:14]=[C:8]([CH:9]([CH3:11])[CH3:10])[C:6]=2[CH:7]=1

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 7918Acetic AnhydrideHCID 10796Cesium carbonateHCID 162206331-(5-Bromo-2-hydroxyphenyl)-2-methylpropan-1-one

Product 1

HCID 594578545-Bromo-3-isopropylbenzo[d]isoxazoleYield 15%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

1-(5-Bromo-2-hydroxyphenyl)-2-methylpropan-1-one (0.82 g, 3.37 mmol) was dissolved in EtOH (10 mL) then hydroxylamine (50% solution in water, 0.267 g, 4.05 mmol) was added followed by HOAc (1 drop). The mixture was heated to about 80° C. for about 2 h. The mixture was cooled then evaporated under reduced pressure to give an oil. Acetic anhydride (2 mL, 20 mmol) was added and the mixture was stirred for about 45 min at ambient temperature. The mixture was concentrated under reduced pressure then pyridine (7 mL) was added and then the mixture was heated to about 145° C. for about 3 h. The mixture was cooled, treated with 1 N HCl, and extracted with EtOAc. The organic extract was dried over MgSO4, filtered and evaporated to a residue that was then dissolved in DME (4 mL). Cesium carbonate (1.09 g, 3.35 mmol) was added and the mixture was heated at about 150° C. for about 30 min in the microwave. The mixture was evaporated and then purified by flash chromatography with 9:1 heptane/EtOAc to give the title compound (0.12 g, 15%): LC/MS (Table 1, Method a) Rt=3.33 min; MS m/z: 340.1 (M+H)+.

Workup

  1. temperatureThe mixture was cooled
  2. customthen evaporated under reduced pressure
  3. customto give an oil
  4. concentrationThe mixture was concentrated under reduced pressure
  5. additionpyridine (7 mL) was added
  6. temperaturethe mixture was heated to about 145° C. for about 3 h
  7. temperatureThe mixture was cooled
  8. additiontreated with 1 N HCl
  9. extractionextracted with EtOAc
  10. extractionThe organic extract
  11. dry with materialwas dried over MgSO4
  12. filtrationfiltered
  13. customevaporated to a residue that
  14. dissolutionwas then dissolved in DME (4 mL)
  15. temperaturethe mixture was heated at about 150° C. for about 30 min in the microwave
  16. customThe mixture was evaporated
  17. custompurified by flash chromatography with 9:1 heptane/EtOAc

Sources & evidence

ORD record
ord-2780b11d2b8c46c1ba8729bf6f35a306
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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