Toward the scale-up of a bicyclic homopiperazine via schmidt rearrangement and photochemical oxaziridine rearrangement in continuous-flow
Leung, Leo M H
Smith, Deborah A
AffiliationDrug Discovery Unit, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park, Macclesfield SK10 4TG
MetadataShow full item record
AbstractThe 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.
CitationBrown M, Aljarah M, Asiki H, Leung LMH, Smithen DA, Miller N, et al. Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine Rearrangement in Continuous-Flow. Org Process Res Dev. 2021;25(1):148-56.
JournalOrganic Process Research and Development
- A photochemical ring expansion of 6- to 8-membered nitrogen heterocycles by [1,3]-sigmatropic rearrangement.
- Authors: Manning MA, Sun W, Light ME, Harrowven DC
- Issue date: 2021 May 6
- Rearrangements of bicyclic nitrones to lactams: comparison of photochemical and modified Barton conditions.
- Authors: Zeng Y, Smith BT, Hershberger J, Aubé J
- Issue date: 2003 Oct 17
- Batch versus flow photochemistry: a revealing comparison of yield and productivity.
- Authors: Elliott LD, Knowles JP, Koovits PJ, Maskill KG, Ralph MJ, Lejeune G, Edwards LJ, Robinson RI, Clemens IR, Cox B, Pascoe DD, Koch G, Eberle M, Berry MB, Booker-Milburn KI
- Issue date: 2014 Nov 10
- Total synthesis of meloscine by a [2+2]-photocycloaddition/ring-expansion route.
- Authors: Selig P, Herdtweck E, Bach T
- Issue date: 2009
- A practical flow reactor for continuous organic photochemistry.
- Authors: Hook BD, Dohle W, Hirst PR, Pickworth M, Berry MB, Booker-Milburn KI
- Issue date: 2005 Sep 16