An Easy, Convenient, and Safe Process for the Synthesis of Lofexidine Hydrochloride

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2021-07-27 DOI:10.1021/acs.oprd.0c00453

Monica Donnola*, Annalisa Airoldi, Alessandro Barozza, Jacopo Roletto, Paolo Paissoni

引用次数: 0

Abstract

A very efficient, cost-effective, and easily scalable process for the synthesis of lofexidine hydrochloride (1), an alpha 2-adrenergic receptor agonist used for treating opioid withdrawal is presented. Process development allows the preparation of lofexidine hydrochloride (1) through a one-pot amidation/imidazoline ring formation reaction, starting from ethyl 2-(2,6-dichlorophenoxy)propionate (13) and ethylenediamine (5) by the action of titanium isopropoxide. The required intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (13) can efficiently be obtained through O-alkylation of 2,6-dichlorophenol (2) with ethyl 2-chloropropionate (12) using potassium carbonate as an acid-scavenger agent.

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一种简单、方便、安全的合成盐酸洛非昔定的工艺

介绍了一种非常高效、经济、易于扩展的合成盐酸洛非昔定的方法(1)，一种用于治疗阿片类药物戒断的α 2-肾上腺素能受体激动剂。工艺开发允许在异丙醇钛的作用下，以2-(2,6-二氯苯氧基)丙酸乙酯(13)和乙二胺(5)为起始原料，通过一锅酰胺化/咪唑啉成环反应制备盐酸洛非昔定(1)。以碳酸钾为酸清除剂，通过2,6-二氯苯酚(2)与2-氯丙酸乙酯(12)的o -烷基化反应，可以高效地得到所需的中间体2-(2,6-二氯苯氧基)丙酸乙酯(13)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.