H-1-{F-19} NOE difference spectroscopy as a tool for structural assignment of positional isomers in fluorine-substituted analogues of FPL 64176

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 H-1 NMR spectra of these compounds. Using H-1-{H-1} and H-1-{F-19} 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.