Pyrrole Chemistry. An Improved Synthesis of Ethyl Pyrrole-2-carboxylate Esters from Diethyl Aminomalonate

Article abstract of DOI:10.1021/jo00350a033

Ethyl pyrrole-2-carboxylates, versatile precursors for the total synthesis of both synthetic model and naturally occurring tetrapyrroles and porphyrins, can be prepared in greatly improved yields by the addition of 1,3-diketones and preformed diethyl aminomalonate to boiling glacial acetic acid.The method is suitable for both small- and large-scale synthesis and has proved far more reliable than the original in situ dissolving zinc reduction of diethyl oximinomalonate discovered by Kleinspehn.Yields range from 60-70percent for the dominant product isomer from unsymmetrical diketones to 75-90percent for the single product derived from symmetrical diketones.Seventeen examples of alkyl-substituted ethyl pyrrole-2-carboxylates are provided.Improved procedures are given for the preparation of the required precursors.