Reagent-free continuous thermal tert-butyl ester deprotection.
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 15-40min 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.
Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, United States. Electronic address: k_cole@lilly.com.
Kevin P
KP
Cole
Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, United States.
Sarah J
SJ
Ryan
Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, United States.
Jennifer McClary
JM
Groh
Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN 46285, United States.
Richard D
RD
Miller
D000596:Amino Acids / Q000737:chemistry; D004952:Esters / Q000737:chemistry*; D006358:Hot Temperature; D011312:Pressure; D012997:Solvents / Q000737:chemistry
D000596:Amino Acids; D004952:Esters; D012997:Solvents
Continuous processing; Flow chemistry; Plug flow reactor; Thermolysis; tert-Butyl ester deprotection