2025/01/29 by Matthew Badland, Maria S. Brown, Nessa Carson +15 · 1 voice
Chemistry · Pharmacology, Toxicology and Pharmaceutics · #Chemical Reactions and Isotopes #Chemical Reactions and Mechanisms #Synthesis and Catalytic Reactions
paper · doi:10.1021/acs.oprd.4c00514
openalex publication_date 2025/01/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/15
The compound ( S )-oxetan-2-ylmethyl tosylate 1 was identified as a key synthetic fragment for the introduction of the 2-substituted oxetane functionality in potential drug candidates under development in our laboratories. The focus of this paper is to highlight methodologies evaluated in our quest for synthetic routes to 2-substituted oxetanes suitable for enabling manufacture. Of the five routes investigated, three (Route 1A, Route 2, and Route 3) were successfully demonstrated in the laboratory. Subsequently, Route 3 was executed at scale to deliver metric ton quantities of the oxetane tosylate 1 as a solution in EtOAc, which was integrated into the synthesis of 2 and aforementioned drug candidates.