An improved process for the preparation of trimethylhydrazine and its coupling with an activated acid intermediate

Trimethylhydrazine (TMH) was prepared in two steps from 1,1-dimethylhydrazine, using an easy to scale-up procedure that avoided difficult acid−base extractions. The procedure provided TMH as a solution in 1,4-dioxane, in a form that was easy and safe to handle in a coupling with an enantiomerically pure, sterically hindered, Boc-protected-amino acid, 1. This key coupling reaction in the preparation of 3 was accomplished through the corresponding acid chloride, thereby avoiding the use of expensive coupling reagents.