Benzene → N-methyl-3-(trifluoromethyl)isoxazol-5-amine

HRID 2291713Notes

Reaction equation

HRID 2291713 reaction equation
[Na].[F:2][C:3]([F:14])([F:13])[C:4]1[CH:8]=[C:7]([NH:9][C:10](=O)C)[O:6][N:5]=1.C1C=CC=CC=1.S(OC)(OC)(=O)=O>CO>[F:14][C:3]([F:2])([F:13])[C:4]1[CH:8]=[C:7]([NH:9][CH3:10])[O:6][N:5]=1

Participants

6

Reactant 4

HCID 241BenzeneHCID 6497Dimethyl SulfateHCID 5360545SodiumHCID 21279278N-(3-(trifluoromethyl)-1,2-oxazol-5-yl)acetamide

Product 1

HCID 15613887N-methyl-3-(trifluoromethyl)isoxazol-5-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium metal (0.28 g, 12.3 mmole) was dissolved in dry methanol (12.3 ml) and to this solution was added 3-trifluoromethyl-5-acetylaminoisoxazole (2.38 g, 12.26 mmole). After stirring at room temperature for 15 minutes, the mixture was concentrated in vacuo and dry benzene (12.3 ml) was added to the residue. The mixture was concentrated in vacuo and dry benzene (18.4 ml) and dimethyl sulfate (1.55 g, 12.3 mmole) were added to the residue, followed by refluxing for 2 hours. After cooling, the precipitated crystals were filtered off. The filtrate was washed with a 8% solution of sodium bicarbonate and concentrated in vacuo. A 5% solution of sodium hydroxide (11.8 g) was added to the residue and the mixture was sitrred at room temperature for 2 hours. It was extracted with methylene chloride and the methylene chloride layer was dried with anhydrous sodium sulfate. The extract was concentrated in vacuo and the resulting residue was recrystallized from cyclohexane to give the title compound as colorless columns. Yield: 1.41 g (65.4%). m.p. 48.5°-50.0° C.

Workup

  1. concentrationthe mixture was concentrated in vacuo and dry benzene (12.3 ml)
  2. additionwas added to the residue
  3. additionwere added to the residue
  4. temperatureby refluxing for 2 hours
  5. temperatureAfter cooling
  6. filtrationthe precipitated crystals were filtered off
  7. washThe filtrate was washed with a 8% solution of sodium bicarbonate
  8. concentrationconcentrated in vacuo
  9. additionA 5% solution of sodium hydroxide (11.8 g) was added to the residue
  10. waitthe mixture was sitrred at room temperature for 2 hours
  11. extractionIt was extracted with methylene chloride
  12. dry with materialthe methylene chloride layer was dried with anhydrous sodium sulfate
  13. concentrationThe extract was concentrated in vacuo
  14. customthe resulting residue was recrystallized from cyclohexane

Sources & evidence

ORD record
ord-922658e9b88644c7ac97f1599d09f410
Source dataset
uspto-grants-1989_01
Patent number
US04797492

Reaction notes

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