Synthesis and configuration of trans‐1‐amino‐4‐benzyl‐2,6‐dimethylpiperazine as an intermediate of semi‐synthetic rifamycins

Abstract
The synthesis of trans‐1‐amino‐4‐benzyl‐2,6‐dimethylpiperazine (1b), trans‐4‐benzyl‐2,6‐dimethylpiperazine (VIIb) and trans‐2,6‐dimethylpiperazine (IIb) are described, by condensation of N‐benzyl‐1,2‐propanediamine with α‐bromopropionate and successive thermal cyclization and reduction with lithium aluminum hydride.The assignment of the cis, trans configuration to the isomers was based on a thorough examination of the ring proton nmr signals of the two isomers of 4‐benzyl‐2,6‐dimethylpiperazine (VIIa and VIIb) interpreted in terms of conformational considerations.