(267b) Development and Implementation of Flow Chemistry for a Curtius Rearrangement

The Curtius rearrangement is the conversion of a carboxylic acid moiety into an amine with retention of stereochemistry via a high energy acyl azide intermediate.  An investigation of the Curtius rearrangement to generate an asymmetric isocyanate (Curtius product) via the acyl azide and reaction of the isocyanate with BnOH will be described.  A flow procedure to produce the Curtius product was developed.   Attempts to conduct the entire sequence from trans acid to amino ester using flow chemistry will be described.  Multikilograms of the amino ester have been produced safely through the Curtius reaction using batch or flow processing in high overall yield.