Development of an Efficient Process to Prepare Methyl 4,5,6-Trichloropicolinate Using Highly Selective C–H Borylation/Chlorodeborylation Reactions

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2022-10-11 DOI:10.1021/acs.oprd.2c00247

Xiaoyong Li*, Eric Wiensch and Jossian Oppenheimer,

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引用次数: 1

Abstract

This report details the development of an efficient process to prepare methyl 4,5,6-trichloropicolinate using Ir-catalyzed C–H borylation followed by CuCl₂-mediated chlorodeborylation under optimized conditions. The process featured extremely low loadings (as low as 0.0005 equiv) of an [Ir(OMe)cod]₂ precatalyst with outstanding reactivity and regioselectivity (>150:1) during C–H borylation. The impurity from product dechlorination can be significantly reduced by >30-fold to <0.4%. The excellent reactivity and control of the protodeborylation impurity in subsequent copper-mediated chlorodeborylation was also highlighted. This enabled successful demonstration of a highly efficient process at a 46 mmol scale with an excellent overall yield (75%). Furthermore, it was showcased that the Ir catalyst and 4,4′-di-tert-butyl-2,2′-bipyridyl (dtbpy) ligand can be directly recycled and reused after filtration of the product. All these developments would offer significant economic benefits as well as process simplification for applying Ir chemistry.

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采用高选择性C-H硼化/氯酰化反应制备4,5,6-三氯吡啶甲酯的高效工艺研究

本文详细介绍了在优化条件下，采用ir催化的C-H硼化反应和cuc2介导的氯酰化反应制备4,5,6-三氯吡啶甲酯的高效工艺。该工艺在C-H硼化过程中具有极低的[Ir(OMe)cod]2预催化剂负载(低至0.0005当量)，具有出色的反应活性和区域选择性(>150:1)。产品脱氯产生的杂质可显著降低30倍至0.4%。在随后的铜介导的氯黛波化反应中，强调了原黛波化杂质的良好反应性和可控性。这使得在46 mmol的规模上成功地演示了一个高效的工艺，总收率(75%)很高。结果表明，Ir催化剂和4,4′-二叔丁基-2,2′-联吡啶(dtbpy)配体经过滤后可直接回收再利用。所有这些发展都将为应用Ir化学提供显著的经济效益和工艺简化。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.