Hydrochloric Acid → Ethyl 5-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]isoxazole-3-carboxylate

Participants

Reaction Steps

To a stirred solution of ethyl 4-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]-2,4-dioxobutanoate (71 g, 149 mmol) in THF (250 mL) and ethanol (500 mL) is added CH3COONa (24.4 g, 298 mmol) and NH2OH.HCl (22.8 g, 328 mmol) at room temperature. After the conversion to the oximes is complete, 6 M HCl solution was added dropwise to reach pH 2 to promote the cyclization. After stirring for 24 hours, Na2HPO4 was added to reach pH 6 and the suspension taken up in ethyl acetate was thoroughly washed with brine and dried over Na2SO4. The solvent was removed and the residue was crystallized from a mixture of MTBE (240 mL) and hexane (180 mL), to provide the title compound (35 g, 49% yield).

Provenance & Evidence