An alternative synthesis of the lipophilic tail portion of abediterol using linear-selective hydroformylation. Issue 8 (21st February 2019)

• Record Type: Journal Article
• Authors: Munday, Rachel H.; Goodman, Louis; Noonan, Gary M.
• Is Part Of: Tetrahedron letters. Volume 60:Issue 8(2019)
• Page Start: 606
• Page End: 609
• Publication Date: 2019-02-21
• Subjects: Hydroformylation -- Process development -- Route design; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2019.01.037
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Application of hydroformylation to the synthesis of a pharmaceutical intermediate. Improved synthesis with fewer impurities formed. Avoids the use of toxic and explosive hydrazine. Abstract: Abediterol is a compound currently in development for the treatment of respiratory disease at AstraZeneca. In this work we employ hydroformylation, an under-utilised reaction in the synthesis of pharmaceutical intermediates, as a key step to access the lipophilic amine portion of this molecule. The route described herein addresses some of the issues identified in the original route. Namely, hazardous materials are avoided and increased levels of control – from a process chemistry point of view – are demonstrated, with isolation of intermediates possible at multiple points in the synthesis. This work provides 'proof-of-concept' for an alternative synthetic route and provides high-quality material using a series of robust transformations.