Mild and Efficient Synthesis of Para-Substituted 2-Hydroxymethyl Piperazine

Abstract: 2-Hydroxymethyl piperazine is a crucial structural unit and essential intermediate in the drug development process. However, there are few reported methods for synthesizing 2- hydroxymethyl piperazine substituted at position 5. Herein, the 2-hydroxymethyl piperazines are synthesized from serine methyl ester hydrochloride and N-Boc-L-amino acids through a four-step reaction of condensation, deprotection, cyclisation, and reduction. This synthetic route has several advantages, including mild reaction conditions, availability of reagents, non-racemic composition, and the potential for gram-scale synthesis. In this study, we present a mild and effective synthetic method for preparing para-substituted 2-hydroxymethyl piperazine.