Reagent-Free Continuous Thermal tert-Butyl Ester Deprotection

Publication date: Available online 10 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kevin P. Cole, Sarah J. Ryan, Jennifer McClary Groh, Richard D. Miller
Continuous processing enables the use of non-standard reaction conditions such as high temperatures and pressures while in the liquid phase. This expands the chemist's toolbox and can enable previously unthinkable chemistry to proceed with ease. For a series of amphoteric amino acid derivatives, we have demonstrated the ability to hydrolyze the tert-butyl ester functionality in protic solvent systems. Using a continuous plug flow reactor at 120–240 °C and 15–40 min reaction times, no pH modification or additional reagents are needed to achieve the desired transformation. The method was then expanded to encompass a variety of more challenging substrates to test selectivity and racemization potential. The acid products were generally isolated as crystalline solids by simple solvent exchange after the deprotection reaction in good to high yield and purity.

Graphical abstract

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