Hydroxyamine hydrochloride → 5-(2-Benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester

Participants

Reaction Steps

To a stirred solution of 4-(2-benzyloxy-phenyl)-2,4-dioxo-butyric acid ethyl ester (3.75 g, 0.01149 mole) in acetic acid (20 mL) was added hydroxylamine hydrochloride (0.878 g, 0.0126 mole) and the resulting mixture was heated to reflux for 3 hours. Volatiles were removed and the resulting residue was diluted with water, basified with sodium bicarbonate solution and extracted with ethyl acetate, washed the ethyl acetate with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 3.42 g (92%) of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester. LCMS: 324.12 (M+1)+, 78.58%. To a stirred solution of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid ethyl ester (1.75 g, 0.00542 mol) in a mixture of THF (30 mL), methanol (15 mL) and H2O (15 mL) was added NaOH (0.651 g, 0.01628 mol) and the resulting mixture was stirred for 2 hours. The reaction mixture was then diluted with cold water. Volatiles were removed by evaporation and the residue was diluted with water acidified with concentrated HCl. The resulting precipitate was isolated by filtration and dried to afford 1.57 g (98%) of 5-(2-benzyloxy-phenyl)-isoxazole-3-carboxylic acid. LCMS: 296.08 (M+1)+, 84.73%

Provenance & Evidence