Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine
Michael Brown1,2, Mohammed Aljarah1,2, Hannah Asiki2
1Drug Discovery Unit, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park, Macclesfield SK10 4TG, United Kingdom.
Abstract:
The scale-up of a chiral bicyclic homopiperazine of pharmaceutical interest was investigated. The outcome and safety profile of a key batch ring-expansion step via Schmidt rearrangement was improved using continuous-flow chemistry. The selectivity of nitrogen insertion for the ring expansion was improved via an alternative photochemical oxaziridine rearrangement under mild conditions, which when converted to continuous-flow in a simple and efficient flow reactor allowed the first photochemical scale-up of a homopiperazine.
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