Development and Execution of an Ni(II)-Catalyzed Reductive Cross-Coupling of Substituted 2-Chloropyridine and Ethyl 3-Chloropropanoate
Development and Execution of an Ni(II)-Catalyzed Reductive Cross-Coupling of Substituted 2-Chloropyridine and Ethyl 3-Chloropropanoate
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DOI：
10.1021/acs.oprd.0c00134
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发表时间：
2020-06-19
影响因子：
3.4
通讯作者：
Vaidyanathan, Rajappa
中科院分区：
文献类型：
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作者：
Nimmagadda, Krishna;Korapati, Satish;Vaidyanathan, Rajappa
我们描述了镍催化的取代的2-氯吡啶和3-氯丙酸乙酯之间的还原性交叉亲电偶联反应，使用锰尘作为末端还原剂的发展和放大。几种添加剂进行了筛选的锰还原剂的活化原位，和氯三乙基硅烷（TESCI）被发现提供最佳的转化率。一个聚焦光束反射测量（FBRM）探头被用来监测颗粒磨损以及锰活化反应过程中。采用建模来获得对混合要求的理解，所述混合要求将确保在放大过程中锰的有效悬浮。该方法在7 kg规模上成功地证明，并以64%的产率得到2。
We describe the development and scale-up of a nickel-catalyzed reductive cross-electrophile coupling reaction between a substituted 2-chloropyridine and ethyl 3-chloropropanoate using manganese dust as the terminal reductant. Several additives were screened for the activation of the manganese reductant in situ, and chlorotriethylsilane (TESCI) was found to provide the optimal conversion. A focused beam reflectance measurement (FBRM) probe was utilized to monitor particle attrition as well as manganese activation during the reaction. Modeling was employed to garner an understanding of mixing requirements that would ensure effective suspension of the manganese during scale-up. The process was successfully demonstrated on a 7 kg scale and afforded 2 in 64% yield.