Triethylamine → 3-(4-Methoxyphenyl)isoxazole-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of pyrrolidine (0.63 mL, 7.5 mmol) in diethyl ether (6 mL) was added during 15 min to a solution of ethyl propiolate (0.76 mL, 7.5 mmol) in diethyl ether (6 mL) at 0° C. with stirring. The resulting solution was stirred for 30 min at rt, whereafter triethylamine (1.04 mL, 7.5 mmol) was added and the reaction was chilled to 0° C. again and a solution of N-hydroxy-4-methoxybenzenecarboximidoyl chloride (1.39 g, 7.5 mmol) in diethyl ether (10 mL) was added during 30 min. The temperature was allowed to go to rt and was washed with 1 M HCl and water, dried (Na2SO4) and evaporated. The crude intermediate was dissolved in acetic acid (3 mL) and conc. HCL (3 mL) and the mixture was refluxed for 2 h. The solvents were evaporated and the mixture was partioned between ethyl acetate and cold aqu. NaOH (0.5 M). The aqueous phase was acidified by conc. HCl and filtered. The crystals were purified by silica gel chromatography (DCM:MeOH 19:1 to 5:1) to give a white solid (45 mg), which was used in the next step without further analysis or purification (ca. 90% pure). MS 220 (M+1).

Provenance & Evidence