Facile Generation of tert-Butoxycarbonyl Chloride Equivalent and Its Use in Microflow Reactor

Abstract

tert-Butyl carbamates, carbonates, and carbonothioates are useful as bioactive compounds, functional polymers, and synthetic intermediates for a variety of valuable organic compounds. The most conventional approach for the preparation of these tert-butoxycarbonyl (Boc)-containing compounds includes a nucleophilic acyl substitution reaction using commercially available and stable di-tert-butyl dicarbonate (Boc 2 O). However, this method usually requires a long reaction time and high-temperature conditions because of the mild electrophilicity of Boc 2 O. The use of highly electrophilic BocCl and its equivalent (BocX) allows the rapid and mild preparation of Boc-containing compounds. However, BocX is unstable, which has hampered its use. Herein, we report a rapid, mild, and facile preparation of BocX from triphosgene, t-BuOH, and two different types of bases, Nmethylmorpholine and N-methylimidazole in a microflow reactor. The in situ-generated BocX was immediately used for the formation of carbamates, carbonates, and a carbonothioate. The role of the two different bases was also investigated. The developed approach showed a significantly better performance than that using Boc 2 O.