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Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine Rearrangement in Continuous-Flow.

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.

SUBMITTER: Brown M

PROVIDER: S-EPMC7928940 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine Rearrangement in Continuous-Flow.

Brown Michael M Aljarah Mohammed M Asiki Hannah H Leung Leo M H LMH Smithen Deborah A DA Miller Natalie N Nemeth Gabor G Davies Lawrence L Niculescu-Duvaz Dan D Zambon Alfonso A Springer Caroline C

Organic process research & development 20201015 1

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 s ...[more]

PMID: 33679122

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