From Paracetamol to Rolipram and Derivatives: Application of Deacetylation–Diazotation Sequences and Palladium-Catalyzed Matsuda–Heck Reaction

Abstract

A six-step synthesis of the antidepressant rolipram from the popular analgetic 4-acetamidophenol (paracetamol) is described. The steps include oxidative functionalization of the aromatic core, diazonium salt formation via deacetylation-diazotation, Matsuda–Heck reaction, conjugate addition of nitromethane, and hydrogenative cyclization.

Key words

acetanilides - deacetylation - diazonium salts - palladium - Matsuda–Heck reaction

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