Diethanolamine Boronic Esters: Development of a Simple and Standard Process for Boronic Ester Synthesis

Herein, we disclose the unique physical
properties of diethanolamine
(DEA) boronic esters that have facilitated the development of a simple
and standard process for their synthesis and isolation using environmentally
sustainable solvents. Moreover, their preparation is facile, robust,
and scalable and can be telescoped from a solution of boronic acid
or boronic ester via esterification/transesterification
with DEA, therefore providing wide access from a plethora of reaction
types. To date, AstraZeneca has successfully manufactured three DEA
boronic esters at the kilogram scale (5, 50, and 100 kg batches),
with plans to expand this to more examples in 2020.

本文披露了二乙醇胺（diethanolamine, DEA）硼酸酯的独特物理性质，此类性质助力开发出一套采用环境友好型溶剂合成与分离该类化合物的简便标准化工艺。此外，该类硼酸酯的制备流程简便易行、稳定性优异且可规模化放大，可直接由硼酸或硼酸酯溶液与二乙醇胺经酯化/转酯化反应串联完成，因此可通过多种反应类型实现其广泛制备。截至目前，阿斯利康（AstraZeneca）已成功以千克级规模（批次分别为5 kg、50 kg与100 kg）生产了三款二乙醇胺硼酸酯，并计划于2020年将该类产品拓展至更多品类。