Synthesis of N-alkylated 4-fluoro-5-phenylpyrrole-2-carboxylate via isolable pyrroline ionic intermediates

Abstract

Organic fluorine chemistry produces many useful products. This paper elucidates the reaction of ethyl-4,4-difluoro-2-iodo-5-oxo-5-phenylpentanoate (2) with primary amines in a one-pot scheme. The reaction produced a series of beta-fluoropyrrole derivatives at ambient temperatures. In this reaction, the less bulky the primary amine the higher was the resultant yield. When (2) and aqueous methylamine (40%) were allowed to react below 0 degrees C, 5-(ethoxycarboxyl)-1-methyl-3,3-difluoro-2-hydroxy-2-phenylpyrrolidine, an intermediate molecule for 2-ethyl-4-flouro-1-methyl-5-phenylpyrrole-2-carboxylate (5), was isolated first. Then, (5) reacted with hydroperchloric acid and acetic anhydride to form 5-(ethoxycarboxyl)-1-methyl-3,3-difluoro-2-phenylpyrrolinium perchlorate (6), which was converted to 2-ethyl-4-flouro-1-methyl-5-phenylpyrrole-2-carboxylate gradually in the presence of a base. Our experiments demonstrate that the formation of 2-ethyl-4flouro-l-methyl-5-phenylpyrrole-2-carboxylate occurs via both one-pot schemes and stepwise pathways, depending on the reaction conditions. The isolation and characterization of the isolated intermediate (6) suggest an anionic pathway for this reaction.