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