Utility of Triethyloxonium Tetrafluoroborate for Chloride Removal during Sarcosine N‐Carboxyanhydride Synthesis: Improving NCA Purity

The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high‐quality making high‐purity sarcosine N ‐carboxyanhydride (Sar‐NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar‐NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar‐NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar‐NCA derived by synthesis or sublimation. The derived monomers enable the controlled‐living polymerization in DMF and provide access to pSar polymers with Poisson‐like molecular weight distribution within a high range of chain lengths (X n 25–200). In conclusion, the reported method can be easily applied to Sar‐NCA synthesis or purification of commercially available pSar‐NCAs and eases access to well‐defined hetero‐telechelic pSar polymers.