Selective Hydrolysis of Ethyl 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate and Ethyl 5,6-Dihydro-4H-pyrrolo[1,2-b]pyrazole-3-carboxylate as a Key Step in the Large-Scale Synthesis of Bicyclic Heteroaryl Carboxyaldehydes

The isomeric mixture of ethyl 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2- and −3-carboxylates (14 and 15), derived from a proline meso-ionic synthon, demonstrated remarkably different stabilities towards alkaline hydrolysis. On that basis, a nonchromatographic, highly efficient method for their large-scale separation was developed. The desired isomer 14 was converted into 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carbaldehyde, a key intermediate in the synthesis of bicyclic heteroaryl-substituted 6-alkylidene penems.