Continuous-Flow Synthesis of the Key Nicergoline Intermediate 10α-Methoxy-9,10-dihydrolyserol via Photomethoxylation

IF 3.3 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2026-10-16 Epub Date: 2026-10-07 DOI:10.1021/acs.oprd.6c00343

Renfu Huang, Jun Yu, Binjie Zhuang, Zhencheng Yan, Guanghai Wei, Liang Zhang, Fuli Zhang

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引用次数: 0

Abstract

At present, the key nicergoline intermediate 10α-methoxy-9,10-dihydrolyserol (3) is predominantly synthesized by photomethoxylation in batch photoreactors, a conventional method plagued by issues such as poor light penetration, low energy efficiency, severe scale-up barriers, and potential safety risks. In this work, a novel continuous-flow photochemical process for manufacturing this intermediate has been developed using a plate-type mesoscale photoreactor. This approach offers substantial advantages over the traditional batch synthesis, including higher yields, shorter reaction time, excellent stereoselectivity, milder conditions, and enhanced scalability. Optimal conditions were found that led to considerably higher productivity, achieving a throughput of up to 0.73 mol/h of 2 with a residence time of only 20 s. The photochemical sequence was demonstrated at the kilogram scale, highlighting its viability, efficiency, and robustness.

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Nicergoline关键中间体- 10α-甲氧基-9,10-二水解丝氨酸的光甲氧基化连续合成

摘要目前，nicergoline关键中间体10α-甲氧基-9,10-二水解丝氨酸(3)的合成主要采用间歇光反应器中光甲氧基化的方法，该方法存在透光性差、能量效率低、放大障碍严重、安全隐患大等问题。在这项工作中，利用板型中尺度光反应器开发了一种新的连续流光化学工艺来制造这种中间体。与传统的间歇合成相比，这种方法具有显著的优势，包括更高的收率、更短的反应时间、出色的立体选择性、更温和的条件和更强的可扩展性。研究发现，最佳条件可显著提高生产效率，在停留时间仅为20 s的情况下，产量可达0.73 mol/h。光化学序列在千克尺度上进行了演示，突出了其可行性、效率和稳健性。

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.