Hydrogen Bromide → 3-(4-Bromo-3-methylphenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole

HRID 910387Notes

Reaction equation

HRID 910387 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)=[CH:4][C:3]=1[CH3:25].N([O-])=O.[Na+].[BrH:30]>O1CCOCC1.O.[Cu]Br>[Br:30][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)=[CH:4][C:3]=1[CH3:25]

Participants

7

Reactant 3

HCID 260Hydrogen Bromide2×HCID 231598243-(4-Amino-3-methylphenyl)-5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazoleHCID 23668193Sodium Nitrite

Product 1

HCID 231598123-(4-Bromo-3-methylphenyl)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 24593copper(I) bromideSolventHCID 312751,4-DioxaneSolvent

Procedure

In a solution of 0.50 g of 3-(4-amino-3-methylphenyl)-5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole in 1.0 ml of 1,4-dioxane and 2.0 ml of water, 1.0 ml of 47% hydrobromic acid was added, and stirred under reflux with heat for 1 hour. Then, the reaction mixture was cooled with ice, and a solution of 0.10 g of sodium nitrite in 1.0 ml of water was slowly added dropwise with stirring at a temperature of 5° C. or less, after the completion of the addition dropwise, continued to stir at the same temperature for further 1 hour. The diazo mixture was slowly added dropwise in a mixture of 1.0 ml of 47% hydrobromic acid and 0.28 g of copper (I) bromide at 60° C. with stirring, after the completion of the addition dropwise, continued to stir at 60° C. for further 2 hours. After the completion of the reaction, 10 ml of water was added in the reaction mixture, extracted with ethyl acetate (20 ml×2), the organic phases together were washed with water, then dehydrated with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with ethyl acetate-hexane (1:10) to obtain 0.43 g of the aimed product as pale yellow crystal.

Workup

  1. temperatureunder reflux
  2. temperaturewith heat for 1 hour
  3. temperatureThen, the reaction mixture was cooled with ice
  4. stirringwith stirring at a temperature of 5° C. or less
  5. additionafter the completion of the addition dropwise
  6. stirringto stir at the same temperature for further 1 hour
  7. stirringwith stirring
  8. additionafter the completion of the addition dropwise
  9. stirringto stir at 60° C. for further 2 hours
  10. additionwas added in the reaction mixture
  11. extractionextracted with ethyl acetate (20 ml×2)
  12. washthe organic phases together were washed with water
  13. dry with materialdried over anhydrous sodium sulfate
  14. distillationthe solvent was distilled off under reduced pressure
  15. customThe residue was purified with silica gel column chromatography that

Sources & evidence

ORD record
ord-919a3b29ffb74a1d93752164410e7dc3
Source dataset
uspto-grants-2011_09
Patent number
US08022089B2

Reaction notes

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