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Greener deprotection pathways: microwave assisted aqueous deprotection of N-Boc amines
José Vidal-Núñez1, Sebastián Morales-Guerrero1, Lars Ratjen2
1Departamento de Química Orgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile Vicuña Mackenna 4860 Santiago 7820436 Chile fzacconi@uc.cl.
Abstract:
The development of sustainable deprotection strategies is crucial for reducing the environmental impact of multi-step syntheses in pharmaceutical and fine chemical production. In this work, we present a rapid microwave-assisted protocol for the deprotection of N-Boc-protected amines using water as the sole solvent, without corrosive acids, organic solvents, or catalysts. The method enables quantitative deprotection of a wide range of substrates in minutes, significantly reducing reaction times compared to conventional methods and improving the overall sustainability of the process. Density functional theory calculations were performed to understand the reaction mechanism and thermodynamic characteristics of the transformation in aqueous media. The protocol demonstrates broad functional-group tolerance and substrate compatibility, offering a simpler, more environmentally friendly alternative to N-Boc deprotection in medicinal chemistry and related synthetic applications.
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