Ir-Catalyzed Borylation as an Efficient Route to a Nicotine Hapten,Organic Process Research & Development

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Ir-Catalyzed Borylation as an Efficient Route to a Nicotine Hapten
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-04-04 00:00:00 , DOI: 10.1021/acs.oprd.8b00053
Janice E. Sieser ₁ , Mark T. Maloney ₁ , Esmort Chisowa ₁ , Steven J. Brenek ₁ , Sebastien Monfette ₁ , John J. Salisbury ₂ , Nga M. Do ₁ , Robert A. Singer ₁

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The process development of a nicotine analog or hapten (1) for conjugation to a protein as an antigen is described. The original process in early development used an Ir-catalyzed borylation reaction to enable rapid derivatization of nicotine with the desired regiocontrol. While the process was very efficient, it required chromatography to meet purity targets. A related process was later developed that possessed crystalline intermediates to better control levels of process-related impurities and heavy metals in 1. This control strategy for 1 was essential due to the strict purity requirements for conjugation of 1 when forming an antigen. In addition, the Ir-catalyzed borylation was studied to enable robust manufacture via this methodology which led to an efficient process for the preparation of 1.

中文翻译：

Ir催化的硼化作用是获得尼古丁半抗原的有效途径

描述了用于与作为抗原的蛋白质缀合的尼古丁类似物或半抗原（1）的方法开发。早期开发中的原始过程使用Ir催化的硼酸酯化反应，以实现具有所需区域控制能力的尼古丁快速衍生。虽然该过程非常有效，但需要色谱法才能达到纯度目标。一个相关的方法后来被开发出具有结晶中间体到过程相关的杂质和在重金属更好的控制水平1。由于对1的缀合具有严格的纯度要求，因此1的控制策略至关重要当形成抗原时。此外，对Ir催化的硼化进行了研究，以使其能够通过该方法稳健地生产，从而导致制备1的有效方法。

更新日期：2018-04-04

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