Hydroxyamine hydrochloride → 3-Trifluoromethyl-4-phenyl-5-aminoisoxazole

HRID 2291698Notes

Reaction equation

HRID 2291698 reaction equation
Cl.[NH2:2][OH:3].[F:4][C:5]([F:18])([F:17])[C:6]([CH:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:9]#[N:10])=O>CO>[F:4][C:5]([F:18])([F:17])[C:6]1[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:9]([NH2:10])[O:3][N:2]=1

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 2776431alpha-(2,2,2-Trifluoroacetyl)benzeneacetonitrile

Product 1

HCID 156138913-Trifluoromethyl-4-phenyl-5-aminoisoxazoleYield 82.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methanol (53 ml) and 96% hydroxylamine hydrochloride (2.82 g, 0.0390 mole, 1.3 eq.) were added to -(trifluoroacetyl)phenylacetonitrile (6.96 g, 0.0300 mole) and the mixture was heated under reflux for 68 hours. After methanol was distilled off under reduced pressure and the resulting residue was neutralized with a 8% solution of sodium bicarbonate, the solution was extracted with methylene chloride. After being dried with anhydrous sodium sulfate, it was concentrated and purified by column chromatography on silica gel to give the title compound (5.62 g, 82.1%). The product was recrystallized from benzene-cyclohexane to recover the title compound (4.80 g, 70.1%) as pale yellow needles, m.p. 89°-91° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 68 hours
  3. distillationAfter methanol was distilled off under reduced pressure
  4. extractionthe solution was extracted with methylene chloride
  5. dry with materialAfter being dried with anhydrous sodium sulfate, it
  6. concentrationwas concentrated
  7. custompurified by column chromatography on silica gel

Sources & evidence

ORD record
ord-16ea8c8d48ee4c5dba9759520f291f74
Source dataset
uspto-grants-1989_01
Patent number
US04797492

Reaction notes

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