METHODS AND SYSTEMS FOR FORMING BORONIC ACIDS AND INTERMEDIATES THEREOF

摘要

Methods for forming boronic acids, and intermediates thereof, are disclosed. The method may include mixing a 1-chloro-2-substituted-3-fluorobenzene starting material with an alkyllithium in a first reactor to form a reaction mixture. The 1-chloro-2-substituted-3-fluorobenzene starting material may react with the alkyllithium to form a lithiated intermediate. The reaction mixture may be continuously transferred to a second reactor and a borate may be continuously introduced to form a boronate. The boronic acids may be formed by treating the boronate with aqueous potassium hydroxide followed by acidification. Such methods may provide continuous formation of the boronic acids and may reduce an amount of a reactive intermediate present during processing as well as cycle times. Systems for forming the boronic acids are also disclosed.