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

摘要

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 non-chromatographic, 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.