Kilogram synthesis of pinoxaden

Abstract An optimized kilogram‐scale synthetic route for pinoxaden was successfully developed. The key intermediate dimethyl 2‐(2,6‐diethyl‐4‐methylphenyl)malonate ( 19 ) was prepared from 2,6‐diethyl‐4‐methylaniline through diazotization reaction, Suzuki cross‐coupling reaction, and alcoholysis reaction in 59% yield over three steps in 97.3% purity. 1,4,5‐Oxadiazepane dihydrobromide ( 11 ) was obtained from diethylene glycol through esterification, cyclization, deprotection, and salification in 64% yield over three steps. Pinoxaden was given by aminolysis of 19 with 11 , followed by acylation by pivaloyl chloride in 64% yield over two steps in 99.9% purity. Purification methods for the intermediates and the final product were developed.