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

被引：4

作者：

Brown, Michael ^{[1
,2
]}

Aljarah, Mohammed ^{[1
,2
]}

Asiki, Hannah ^{[2
]}

Leung, Leo M. H. ^{[1
,2
]}

Smithen, Deborah A. ^{[1
,2
]}

Miller, Natalie ^{[2
]}

Nemeth, Gabor ^{[2
]}

Davies, Lawrence ^{[2
]}

Niculescu-Duvaz, Dan ^{[1
,2
]}

Zambon, Alfonso ^{[2
]}

Springer, Caroline ^{[1
,2
]}

机构：

[1] Univ Manchester, Canc Res UK Manchester Inst, Drug Discovery Unit, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[2] Canc Res UK Ctr Canc Therapeut, Inst Canc Res, London SM2 5NG, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2021年 / 25卷 / 01期

基金：

英国惠康基金;

关键词：

homopiperazine; continuous-flow; Schmidt; oxaziridine; photochemical; microreactor; REGIOSELECTIVE FUNCTIONALIZATION; BECKMANN REARRANGEMENT; ACID; KETONES; REACTOR; PREFERENCES; GENERATION; LIGHT; UV;

D O I：

10.1021/acs.oprd.0c00361

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页码：148 / 156

页数：9

共 46 条

[1] Oxaziridine rearrangements in asymmetric synthesis [J].