Phenylacetaldehyde → N-benzyl-2-(3-benzylisoxazol-5-yl)-4-methylthiazole-5-carboxamide

Participants

Reaction Steps

To a solution of 2-phenylacetaldehyde (0.05 mL, 0.44 mmol) in t-butanol (2.5 mL) and water (2.5 mL) was added hydroxylamine hydrochloride (0.03 g, 0.45 mmol) and sodium hydroxide (0.02 g, 0.50 mmol). The reaction mixture was stirred at ambient temperature for 3 hours, followed by the addition of chloramine T (0.14 g, 0.50 mmol), N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamide (0.10 g, 0.39 mmol) and copper(I) iodide (0.01 g, 0.06 mmol). The reaction mixture was stirred for 18 hours at ambient temperature and extracted with ethyl acetate, washed with 10% ammonium chloride solution and brine. The organic solution was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound as a white solid (0.08 g, 53%): mp 103-104° C.; 1H NMR (300 MHz, CDCl3) δ 7.36-7.17 (m, 10H), 6.60 (s, 1H), 6.55 (t, J=5.6 Hz, 1H), 4.56 (d, J=5.6 Hz, 2H), 4.01 (s, 2H), 2.67 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.2, 163.2, 161.1, 156.8, 152.8, 137.5, 136.5, 128.9, 128.8, 127.8, 127.2, 103.1, 44.3, 32.3, 17.3; MS (ES+) m/z 390.3 (M+1).

Provenance & Evidence