Hydroxyamine hydrochloride → Ethyl 5-(2-(trifluoromethyl)phenyl)isoxazole-4-carboxylate

HRID 474358Notes

Reaction equation

HRID 474358 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C:5]([C:10](=[O:21])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([F:20])([F:19])[F:18])=[CH:6][N:7](C)C)[CH3:2].Cl.NO>CO>[CH2:1]([O:3][C:4]([C:5]1[CH:6]=[N:7][O:21][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([F:20])([F:19])[F:18])=[O:22])[CH3:2]

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 540427953-Dimethylamino-2-(2-trifluoromethyl-benzoyl)-acrylic acid ethyl ester

Product 1

HCID 20297498Ethyl 5-(2-(trifluoromethyl)phenyl)isoxazole-4-carboxylateYield 51.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-dimethylamino-2-(2-trifluoromethyl-benzoyl)-acrylic acid ethyl ester (3.10 g, 9.80 mmol, 1.0 equiv) and hydroxylamine hydrochloride (683 mg, 9.80 mmol, 1.0 equiv) in methanol (25 mL) was heated to reflux for 90 minutes. After cooling, the mixture was partitioned between water and ethyl acetate and separated. The aqueous layer was extracted with ethyl acetate. The combined organic extracts was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Purification by flash column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane) gave 1.43 g (51%) of 5-(2-trifluoromethyl-phenyl)-isoxazole-4-carboxylic acid ethyl ester. 1H NMR (300 MHz, CDCl3) δ: 8.38 (s, 1H), 7.69 (d, 1H), 7.61-7.47 (m, 2H), 7.27 (d, 1H), 3.93 (br, 2H), 0.87 (br, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 90 minutes
  3. temperatureAfter cooling
  4. customthe mixture was partitioned between water and ethyl acetate
  5. customseparated
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic extracts was washed with saturated aqueous sodium chloride
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customPurification by flash column chromatography on silica gel (gradient: 0 to 30% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-6529b7cc8f27482e819a06fca576e731
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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