Organic Chemistry

Improved Access to Cyclopropanol via Supply-Centered Synthesis



Access to cyclopropanol is improved by developing a route from highly available, cyclopropyl methyl ketone. The Baeyer-Villiger oxidation inserts oxygen between the cyclopropyl and ketone functionalities, and the alcohol is subsequently unmasked by cleaving the ester with an amine. Optimization resulted in high yield (>90% for each step), isolation of volatile and water soluble cylopropanol, selection of a peroxide with improved safety profile (urea hydrogen peroxide, UHP), and implementation of continuous flow to handle an exotherm. The urea present in the peroxide unexpectedly enhanced conversion of the ketone to the ester, and the addition of a rheology modifier to a 20 wt% suspension of UHP in DCM facilitated continuous delivery of an otherwise difficult to pump slurry.


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