Hydrochloric Acid → 5-(3,5-Dimethyl-benzylcarbamoyl)-thiophene-3-carboxylic acid ethyl ester

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Reaction Steps

0.5 g 2-carboxy-thiophen-4-carboxylic acid ethyl ester (M. Janda, J. Srogl, M. Nemec, I. Stibor; Org. Prep. and Proced. Int. 3 (6) (1971) 295.) and 0.67 g N′-(3-dimethylaminopropyl)-N-ethylcarbodiimid×HCl are stirred in 50 mL DCM for 15 min. Then, 0.338 g 3,5-dimethylbenzylamin are added and the mixture is stirred overnight. The solution is extracted with 2N HCl and water, then evaporated. The residue is titurated with isohexan, and the resulting crystals are filtrated and air-dried, yielding 0.58 g (73%) crude 5-(3,5-Dimethyl-benzylcarbamoyl)-thiophene-3-carboxylic acid ethyl ester (7b). This ester in converted to title compound by reaction with hydroxylamine hydrochloride in a manner similar to that described for the conversion of 4b into 4a in example 4. After chromatography (silica, ethylacetate), thiophene-2,4-dicarboxylic acid 2-(3,5-dimethyl-benzylamide) 4-hydroxyamide (7a) is obtained as crystals; 44 mg, 9%, mp: 181° C. (decomp.).

Provenance & Evidence