Formation of a cyclic derivative of ethacrynic acid with diazomethane

Samples of ethacrynic acid were treated with methanol-hydrochloric acid or with diazomethane. GLC and mass spectrometric analysis indicated that the methanol-hydrochloric acid reaction gave the expected methyl ester, whereas diazomethane treatment gave a compound containing an additional 14 mass units. Accurate mass measurement and PMR and IR spectra showed that this product was a cyclic derivative of the methyl ester of ethacrynic acid, methyl 4-(2,3-dihydro-4-ethyl-5-furyl)-2,3-dichlorophenoxyacetate. Either derivatization method can be used for development of an assay for ethacrynic acid.