A Practical and Scalable Process for the Preparation of 4-Aminophenylboronic Acid Pinacol Ester

Abstract

A practical process has been developed for scalable preparation of 4-aminophenylboronic acid pinacol ester through facile two-step procedure. After boron trifluoride etherate efficiently activated the reaction of 4-bromoaniline with diphenyl ketone, metalation reaction of protected 4-bromoaniline with lithium trialkylmagnesiate readily proceeded under mild conditions (−20 °C), which was subsequently subjected to esterification and deprotection reaction to give the 4-aminophenylboronic acid pinacol ester. The improved synthetic route has been successfully scaled up to kilogram quantities in good yield and high quality.Arylboronic acids and arylboronates have shown great importance due to their widespread applications in organic synthesis and other fields. 1,2 In particular, functionalized arylboronic acids and arylboronates are highly valuable because consecutive cross-coupling is possible from these compounds, which can rapidly construct the complex structure of target molecules. 3 Of these compounds, 4-aminophenylboronic acid pinacol ester is one of important arylboronates for its versatile applications in a wide variety of biologically active compounds, 4 for example piperazine-substituted s-triazine derivatives exhibiting various types of biological properties, such as antiHIV, antituberculosis, anticancer, antimycobacterial, etc. 5 In addition, the compound has also been successfully applied in synthesis of fluorescent sensors for heavy and soft metal ions such as mercury. 6 Up to now, some successes have been made in the preparation of 4-aminophenylboronic acid pinacol ester, 7 typical examples included Raj's Pd-catalyzed