• Toward the scale-up of a bicyclic homopiperazine via schmidt rearrangement and photochemical oxaziridine rearrangement in continuous-flow

      Brown, Michael; Aljarah, Mohammed; Asiki, H.; Leung, Leo M H; Smithen, Deborah A | |Miller, N.; Nemeth, G.; Davies, L.; Niculescu-Duvaz, Dan; Zambon, A.; Springer, Caroline; et al. (2021)
      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.