H-19F NOE difference spectroscopy as a tool for structural assignment of positional isomers in fluorine-substituted analogues of FPL 64176

Abstract

Two difluorinated analogues of FPL 64176 (methyl 4-(2-benzylbenzoyl)-2,5-dimethylpyrrole-3-carboxylate) have been synthesized in three steps from 6-fluorophthalide and methyl 2,5-dimethylpyrrole-3-carboxylate. Significant overlap of signals was observed in the aromatic regions of the 1H NMR spectra of these compounds. Using 1H- 1H and 1H- 19F NOE difference spectroscopy it was possible to identify and assign all aromatic resonances and, based on the NOEs observed, differentiate between the positional isomers and definitely assign the structure of each.