Telescoped lithiation, C-arylation and methoxylation in flow-batch hybrid toward the synthesis of canagliflozin. (12th October 2021)

• Record Type: Journal Article
• Authors: Polterauer, Dominik; Williams, Jason D.; Hone, Christopher A.; Oliver Kappe, C.
• Is Part Of: Tetrahedron letters. Volume 82(2021)
• Publication Date: 2021-10-12
• Subjects: Gliflozins -- Canagliflozin -- Flow chemistry -- Continuous processing -- Organolithium -- Flash chemistry; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2021.153351
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Abstract: We report a highly efficient three-step flow-batch hybrid procedure for the synthesis of a key canagliflozin intermediate. The telescoped process provides exquisite control over an exothermic and mixing sensitive lithiation and subsequent C-arylation within a microstructured flow reactor. Methoxylation reagents are then added in flow, before reaching completion in a batch vessel. The flow process afforded the target intermediate in 76% yield, with a throughput of 26.8 g/h.