Process Development and Pilot Plant Scale Synthesis of Spiro[3.5]nonane-6,8-dione

Abstract

A two step synthesis of spiro[3.5]nonane-6,8-dione is reported which allows the production of the target molecule on a pilot plant scale. The first step of the process comprises the epoxidation of spiro[3.5]non-7-en-6-one mediated by sodium perborate. Here, the use of sodium perborate proved beneficial over the standard protocols employing hydrogen peroxide since a much safer process was accomplished. The resulting crude epoxide was subsequently submitted to a palladium-catalyzed rearrangement to afford spiro[3.5]nonane-6,8-dione in 26% overall yield.

Large-Scale Oxidations in the Pharmaceutical Industry

“…Epoxidation of enone 152 generated epoxyketone 153 , which underwent Noyori's Pd-catalyzed epoxide rearrangement to generate 1,3-diketone 154 (Scheme ). On lab scale, the epoxidation was effected with basic hydrogen peroxide in methanol.…”

A mild, large-scale synthesis of 1,3-cyclooctanedione: expanding access to difluorinated cyclooctyne for copper-free click chemistry

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