The diagram shows the PTC C-alkylation of ethyl N-(diphenylmethylene) glycinate. The PTC C-alkylation of this compound is a common reaction that we discuss multiple times in our 2-day PTC course, mostly with chiral phase-transfer catalysts.
This patent uses cesium carbonate as the base. In the various PTC C-alkylations we discuss in the course using the ethyl ester and t-butyl ester of N-(diphenylmethylene) glycinate, the variety of bases used includes 50% NaOH, 50% KOH, cesium carbonate and cesium hydroxide.
The pKa of the active CH2-group is 19. Since that pKa is within the pKa range of 16-23 for which PTC excels for C-alkylation (see the Halpern pKa Guidelines), we do not need unusually strong base to perform the reaction. Thus, we speculate that the reason that some inventors and authors use cesium carbonate may be to attempt to avoid or minimize hydrolysis of the ester before complete C-alkylation is achieved. However, there are definitely several patents and publications that use aqueous NaOH or KOH and are able to avoid hydrolysis and are even able to avoid racemization of the optically active product of the chiral PTC reactions.
We do not know if the inventors of this patent attempted to use NaOH or KOH but if they didn’t, they should have tried it to save money if they would scale up this reaction beyond the 50 g scale of starting material they reported.
It is not clear from the reported workup procedure if the tetrabutylammonium salt was separated from the intermediate after the acid catalysis. We speculate that the quat salt carried through to the reaction with the di-t-butyl dicarbonate and possibly aided in that N-acylation as well
Now contact Marc Halpern of PTC Organics to achieve low-cost high-performance green chemistry by integrating our highly specialized expertise in industrial phase-transfer catalysis with your commercial goals, especially for PTC-base reactions.
