Mitigating the Risk of Coprecipitation of Pinacol during Isolation from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Boron Pinacol Esters: Use of Modeling for Process Design
Mitigating the Risk of Coprecipitation of Pinacol during Isolation from Telescoped Miyaura Borylation and Suzuki Couplings Utilizing Boron Pinacol Esters: Use of Modeling for Process Design
复制标题
使用硼频哪醇酯降低从伸缩式宫浦硼化和铃木耦合分离过程中频哪醇共沉淀的风险：使用建模进行工艺设计
DOI：
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
D. Kjell
中科院分区：
文献类型：
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作者：
J. M. Merritt;M. Andiappan;M. Pietz;Rachel N. Richey;K. A. Sullivan;D. Kjell
在Abemaciclib中间体的开发性合成中，使用双（频哪醇合）二硼（BisPin）对Miyaura硼化和Suzuki偶联反应进行了工艺定义和优化，导致在分离过程中意外地发生频哪醇共沉淀。热力学相分离，蒸馏，和频哪醇相图模型被用来指导一个修改的过程，以保持频哪醇完全可溶的设计。采用质量设计（QbD）方法说明控制策略，并提供最大限度灵活的生产工艺，以保持中间体的高纯度。不同的可能表示的设计空间，以减轻频哪醇沉淀进行了讨论和比较。频哪醇沉淀的风险可能不是研究系统所独有的，并且可能对这类反应的发展具有广泛的影响。
Process definition and optimization of a telescoped Miyaura borylation and Suzuki coupling reaction employing bis(pinacolato)diboron (BisPin), used in the developmental synthesis of an intermediate for Abemaciclib, led to the unexpected coprecipitation of pinacol during the isolation. Thermodynamic phase separation, distillation, and pinacol phase diagram models were used to guide the design of a modified process to maintain pinacol fully soluble. A Quality by Design (QbD) approach was used to illustrate the control strategy and provide a maximally flexible process for manufacturing to maintain high purity of the intermediate. Different possible representations of the design space to mitigate pinacol precipitation are discussed and compared. The risk of pinacol precipitation may not be unique to the system of study and could have broad implication to the development of this class of reactions.
影响因子：
16.6
作者：
Billingsley, Kelvin L.;Barder, Timothy E.;Buchwald, Stephen L.
通讯作者：
Buchwald, Stephen L.