Hydrochloric Acid → N-(3-(trifluoromethyl)-1,2-oxazol-5-yl)acetamide

HRID 2291712Notes

Reaction equation

HRID 2291712 reaction equation
N1C=CC=CC=1.[F:7][C:8]([F:16])([F:15])[C:9]1[CH:13]=[C:12]([NH2:14])[O:11][N:10]=1.[C:17](Cl)(=[O:19])[CH3:18].[OH-].[Na+].Cl>CO.C1C=CC=CC=1.O>[F:7][C:8]([F:16])([F:15])[C:9]1[CH:13]=[C:12]([NH:14][C:17](=[O:19])[CH3:18])[O:11][N:10]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 139139963-(Trifluoromethyl)-1,2-oxazol-5-amine

Product 1

HCID 21279278N-(3-(trifluoromethyl)-1,2-oxazol-5-yl)acetamideYield 81.7%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Dry benzene (56 ml) and pyridine (11.85 g, 150 mmole) were added to 3-trifluoromethyl-5-aminoisoxazole (9.12 g, 60.0 mmole) and the mixture was cooled. Acetyl chloride (10.37 g, 132 mmole) was added dropwise to the mixture, while keeping it below 10° C. After being added dropwise, the mixture was stirred with ice cooling for 10 minutes and at room temperature for 1 hour. Water (60 ml) was added and it was stirred for an additional hour. Benzene (60 ml) was added and the mixture was separated. The benzene layer was washed successively with 2% hydrochloric acid (60 ml) and a 8% solution of sodium bicarbonate and the solvent was evaporated under reduced presssure. Methanol (120 ml) and sodium hydroxide (4.80 g 120 mmole) were added to the residue and the mixture was stirred overnight at room temperature. After being neutralized with conc. hydrochloric acid, the solvent was evaporated under reduced pressure and the resulting residue was dissolved by the addition of benzene (100 ml) and ethyl acetate (20 ml). This solution was washed with water (60 ml) and the solvents were evaporated under reduced pressure to give 3-trifluoromethyl-5-acetylaminoisoxazole (9.51 g) as crystals. This product was recrystallized from benzene to give colorless plates. Yield: 5.67 g, m.p. 108.5°-109.5° C.

Workup

  1. temperaturethe mixture was cooled
  2. customit below 10° C
  3. additionAfter being added dropwise
  4. stirringit was stirred for an additional hour
  5. customthe mixture was separated
  6. washThe benzene layer was washed successively with 2% hydrochloric acid (60 ml)
  7. customa 8% solution of sodium bicarbonate and the solvent was evaporated under reduced presssure
  8. stirringthe mixture was stirred overnight at room temperature
  9. customthe solvent was evaporated under reduced pressure
  10. dissolutionthe resulting residue was dissolved by the addition of benzene (100 ml) and ethyl acetate (20 ml)
  11. washThis solution was washed with water (60 ml)
  12. customthe solvents were evaporated under reduced pressure

Sources & evidence

ORD record
ord-e1c7f767303e4c1f8d61d9c0854aa30f
Source dataset
uspto-grants-1989_01
Patent number
US04797492

Reaction notes

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