Development and Scale-Up of a Regioselective Functionalization of 2-Cyano-3-fluoropyridine in a Flow Reactor

IF 3.3 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2026-08-21 Epub Date: 2026-08-11 DOI:10.1021/acs.oprd.6c00156

Léna Brassart, Antoine Coeuillas, Maxime Manneveau, Thomas Poisson, Julien Legros, Philippe Huez, Massimiliano Forcato, Philippe Jubault, Laëtitia Chausset-Boissarie

引用次数: 0

Abstract

A continuous-flow process was developed for the regioselective functionalization of 2-cyano-3-fluoropyridine using Corning advanced-flow reactors. The flow setup enabled the controlled generation of a pyridyllithium intermediate through deprotonation with lithium diisopropylamide (LDA) under noncryogenic conditions (−20 °C) with a short residence time of 6 s. Subsequent in-line trapping with electrophiles afforded the corresponding highly functionalized pyridine derivatives in high yields and excellent selectivity. The optimized process was seamlessly scaled up using a Corning advanced-flow reactor G1, maintaining high selectivity while achieving a throughput of 83 g.h^–1.

Abstract Image

查看原文本刊更多论文

流动反应器中2-氰基-3-氟吡啶区域选择性功能化的开发与规模化

采用康宁先进流动反应器，开发了2-氰基-3-氟吡啶连续流区域选择性功能化工艺。该流动装置能够在非低温条件下（- 20°C）通过与二异丙酰胺锂（LDA）脱质子生成吡啶锂中间体，停留时间短，为6 s。随后与亲电试剂的在线捕获提供了相应的高功能化吡啶衍生物，收率高，选择性好。优化后的工艺使用康宁先进流动反应器G1进行无缝扩展，在保持高选择性的同时实现83 g.h-1的吞吐量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.