Green chemistry alternatives for an established industrial process of an active pharmaceutical ingredient (API)

Abstract

In this research, an effort was made to improve the protection of a starting molecule used in the industrial process for the synthesis of an API. Three protecting groups were utilized, 2- (Trimethylsilyl)ethoxymethyl Chloride (SEM-Cl), Di-tert-butyl Dicarbonate (BOC2O), and Pivaloyloxymethyl Chloride (POM-Cl). Trials were conducted with each group, even attempting to optimize the preexisting reactions, however, only the ones for BOC2O gave good results. The optimization attempt for the SEM-Cl protection failed as the catalyst available to us was not strong enough for the reaction, while no optimization was possible for the POM-Cl as the best catalyst was already being used, and no alternative was available. After analyzing all final purified products with 1H-NMR, IR, and GC, it was clear that the optimized BOC2O protections, despite working well, still contained quite some impurities. However, in comparison to the trials with the other protecting groups, the modified BOC2O trials were still the best alternatives out of all. Ultimately, the results gathered during this research gave an insight to potential alternatives to the industrial synthesis of this API. Furthermore, findings from this research could also be utilized in the optimization of other industrial processes that make use of similar reactions.