One Step Continuous Flow Synthesis of Highly Substituted Pyrrole-3-Carboxylic Acid Derivatives via in situ Hydrolysis of tert-Butyl Esters

摘要

The first one-step, continuous flow synthesis of pyrrole-3-carboxylic acids directly from tert-butyl acetoacetates, amines and 2-bromoketones is reported. The HBr generated as a by-product in the Hantzsch reaction was utilized in the flow method to saponify the t-butyl esters in situ to provide the corresponding acids in a single microreactor. The protocol was used in the multistep synthesis of pyrrole-3-carboxamides, including two CB1 inverse agonists, directly from commercially available starting materials in a single continuous process.