Hydrochloric Acid → 3-(1-(2-fluorobenzyl)-5-(5-fluoropyridin-2-yl)-1H-pyrazol-3-yl)isoxazole

Participants

Reaction Conditions

Reaction Steps

To a cold solution of 1-(5-fluoropyridin-2-yl)ethanone (1 equiv.) in toluene (9.6 ml) at 0° C., was added 1M LiHMDS in toluene (1 equiv.). The mixture was stirred at 0° C. for 5 min. To this mixture, was added a solution of isoxazole-3-carbonyl chloride (1 equiv.) in toluene (4.8 ml). The mixture was removed from the ice bath and stirred at 25° C. for 5 min. To this mixture, were added 6 N HCl (1 equiv.), followed by (2-fluorobenzyl)hydrazine hydrochloride (1 equiv.) and ethanol (5 ml). The mixture was heated to 100° C. for 2 h. The mixture was cooled to 25° C. and concentrated under vacuum to give a thick red oil. The oil was purified by column chromatography (0 to 35% ethyl acetate in hexanes) to give 3-(1-(2-fluorobenzyl)-3-(5-fluoropyridin-2-yl)-1H-pyrazol-5-yl)isoxazole (13% yield) as a clear film and its regioisomer 3-(1-(2-fluorobenzyl)-5-(5-fluoropyridin-2-yl)-1H-pyrazol-3-yl)isoxazole (14% yield) as a white solid.

Provenance & Evidence