A reagent for safe and efficient diazo-transfer to primary amines: 2-azido-1,3-dimethylimidazolinium hexafluorophosphate

We performed this reaction on a complex alkyl amine/amino acid residue (VH032) to generate the corresponding azide - considerable more complex than the examples in the paper. We found the experiment to be exteremly sensitive to what base you use i.e. it works with Et3N but not DIPEA, significant side-product identified within the paper was observed when using DIPEA. The reaction proceeded without epimerisation of the adjacent stereocentre and worked in the presence of a secondary alcohol. The largest scale we performed this reaction on was ~1 g and the yield was consistent (~70%). At larger scale we made a solution of the azide transfer reagent, cooled the reaction to 0 and added via syringe pump over 30 min. Chemists at a CRO partner have performed this same reaction at ~13 g scale with similar success.