Sodium hydride → 5-(3-(Pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole

Participants

Reaction Steps

To a solution of ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate (13.6 g, 62.5 mmol) and (Z)—N′-hydroxy-4-methylbenzimidamide (9.68 g, 62.5 mmol) in N,N-dimethylformamide (210 mL) cooled in an ice-bath was added 60% sodium hydride (6.25 g, 156 mmol) portion-wise. After the addition, the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was concentrated, water (500 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The solid was collected vacuum filtration, triturated with methanol, and re-collected to give 5-(3-(pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole (17.8 g, 93% yield) as a solid. The compound had an HPLC retention time=3.86 minutes (YMC-Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=305+. 1H NMR (400 MHz, CDCl3) δ ppm 2.46 (s, 3H), 7.35 (d, J=8.28 Hz, 2H), 7.41-7.47 (m, 1H), 7.83-7.91 (m, 2H), 8.09 (d, J=8.28 Hz, 2H), 8.20 (d, J=8.03 Hz, 1H), and 8.76 (d, J=5.02 Hz, 1H).

Provenance & Evidence