Triethylamine → Ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate

Participants

Reaction Steps

To a suspension of the (Z)—N-hydroxypicolinimidoyl chloride (Preparation 63A, 8.00 g, 51.1 mmol) in dichloromethane (75 mL) in a three neck 1000 mL flask immersed in water and equipped with an addition funnel and thermometer was added ethyl propiolate (5.21 mL, 51.1 mmol). A mixture of triethylamine (8.55 mL, 61.3 mmol) and dichloromethane (20 mL) were added to the addition funnel and then slowly added to the reaction dropwise so that the temperature remained between 20 and 28° C. (by adding ice to the water bath). After the triethylamine was completely added, the reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with ethyl acetate (350 mL), washed with water, and washed with brine. The combined aqueous layers were extracted with ethyl acetate, and the combined organic layers were dried over anhydrous magnesium sulfate. Concentration under reduced pressure followed by purification on silica gel using a 20% mixture of ethyl acetate in hexane afforded ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate (9.90 g, 45.4 mmol, 89% yield) as an off white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (t, 3H), 4.47 (q, J=7.26 Hz, 2H), 7.39 (ddd, J=7.59, 4.84, 1.21 Hz, 1H), 7.59 (s, 1H), 7.83 (td, J=7.81, 1.76 Hz, 1H), 8.13 (dt, J=7.92, 1.10 Hz, 1H), and 8.71 (ddd, J=4.84, 1.76, 0.88 Hz, 1H).

Provenance & Evidence