One pot synthesis of 5-substituted isoxazole-3-carboxylic acid methyl ester series compounds
A series of 5-substituted isoxazol-3-carboxylate methyl esters with different substituents were synthesized from β-dicarbonyl compounds,which were prepared firstly from Claisen condensation reaction of substituted methyl ketones and dimethyl oxalate using sodium methanol as base catalyst,then neutralized by concentrated sulfuric acid,reacted with hydroxylamine hydrochloride to obtain oximes,and finally formed a ring at high temperature.The structure of the products was confirmed by 1HNMR,13CNMR and MS,while the reaction conditions of alkali catalyst,solvent and acid neutralization in the synthesis process were optimized,with the differences among synthesis processes of 5-substituted isoxazol-3-methyl carboxylate compounds with different substituents discussed.The results showed that 26 5-substituted isoxazol-3-carboxylate methyl esters were successfully synthesized by one-pot method,of which 23 could be prepared in a single solvent methanol.Without separation and purification of intermediate products,it was simple and carried out only in a single solvent,which could be easily recovered.Among the products,5-tert-butylisooxazol-3-carboxylate methyl ester(Ⅳc),5-(4-aminophenyl)isooxazol-3-carboxylate methyl ester(Ⅳm)and 5-(3-aminophenyl)isooxazol-3-carboxylate methyl ester(Ⅳn)required potassium tert-butoxide as base catalyst and tetrahydrofuran as solvent for synthesis,while the synthesis of 5-trifluoromethylisooxazol-3-carboxylate methyl ester(Ⅳv)was unsuccessful,and further development of synthesis technology and optimization conditions were needed.
one-pot methodisoxazole-3-carboxylatesisoxazolesynthesiscarboxylic acidsfine chemical intermediates
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