Stereoselective Synthesis of Mirogabalin via 1,4-Selective Addition of Lithioacetonitrile to Alkylidene Malonate

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-02-07 DOI:10.1021/acs.oprd.4c00510

Hidenori Ochiai, Taiki Mihara, Miwa Sasagawa, Akira Nishiyama

引用次数: 0

Abstract

The synthesis of mirogabalin was studied for industrial production and an alternative to Daiichi–Sankyo’s method was established. The developed synthesis involves the introduction of a two-carbon unit with the stereoselective 1,4-selective addition of lithioacetonitrile to alkylidene malonate and one-carbon degradation by the Hofmann rearrangement. The precursor for the Hofmann rearrangement was readily prepared from the 1,4-adduct via a one-pot reaction involving decarboxylation, hydrolysis, and hydration.

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丙二酸烷基二烯与乙腈1,4选择性加成立体选择性合成米罗巴林

研究了米洛巴林的工业化合成方法，并建立了一种替代第一-三共法的方法。所开发的合成方法包括引入一个二碳单元，通过立体选择性1,4选择性地将锂乙腈加成到丙二酸烷基腈上，并通过霍夫曼重排进行一碳降解。霍夫曼重排的前体很容易从1,4-加合物中通过脱羧、水解和水合反应制备。

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.