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Updated: Nov 6, 2025
Supercritical Nitrogen Processing for the Purification of Reactive Porous Materials
Published on: May 15, 2015
Solvent-free N-Boc deprotection by ex situ generation of hydrogen chloride gas
Rik H Verschueren1, Philippe Gilles1, Seger Van Mileghem1
1KU Leuven, Department of Chemistry, Molecular Design and Synthesis, Celestijnenlaan 200F - box 2404, B-3001 Leuven, Belgium. wim.deborggraeve@kuleuven.be.
Abstract:
An efficient, scalable and sustainable method for the quantitative deprotection of the tert-butyl carbamate (N-Boc) protecting group is described, using down to near-stoichiometric amounts of hydrogen chloride gas in solvent-free conditions. We demonstrate the ex situ generation of hydrogen chloride gas from sodium chloride and sulfuric acid in a two-chamber reactor, introducing a straightforward method for controlled and stoichiometric release of HCl gas. The solvent-free conditions allow deprotection of a wide variety of N-Boc derivatives to obtain the hydrochloride salts in quantitative yields. The procedure obviates the need for any work-up or purification steps providing an uncomplicated green alternative to standard methods. Due to the solvent-free, anhydrous conditions, this method shows high tolerance towards acid sensitive functional groups and furnishes expanded functional group orthogonality.
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