Continuous-flow synthesis of 7-methoxy-1-tetralone: an important intermediate of (-)-Dezocine

IF 2 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Journal of Flow Chemistry Pub Date : 2023-07-27 DOI:10.1007/s41981-023-00274-0

Liangchuan Lai, Liang Gao, Minjie Liu, Yongxing Guo, Dang Cheng, Meifen Jiang, Fener Chen

{"title":"Continuous-flow synthesis of 7-methoxy-1-tetralone: an important intermediate of (-)-Dezocine","authors":"Liangchuan Lai, Liang Gao, Minjie Liu, Yongxing Guo, Dang Cheng, Meifen Jiang, Fener Chen","doi":"10.1007/s41981-023-00274-0","DOIUrl":null,"url":null,"abstract":"<div><p>\nContinuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":630,"journal":{"name":"Journal of Flow Chemistry","volume":"13 4","pages":"375 - 383"},"PeriodicalIF":2.0000,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Flow Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s41981-023-00274-0","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Continuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process.

Graphical abstract

Abstract Image

查看原文本刊更多论文

7-甲氧基-1-四氢萘酮的连续流动合成

连续流技术已被广泛应用于活性药物成分（API）的生产。在此，我们报告了一种快速的多步连续流策略，用于高效、高产地流动合成 7-甲氧基-1-四氢萘酮，它是阿片类镇痛药 (-)-dezocine 的重要中间体。与传统的间歇式操作相比，这项工作体现了连续流化学的显著优势，如反应时间大大缩短、反应效率大幅提高、反应优化条件控制良好等。与间歇式工艺（即产率 50%、纯度 92%）相比，该工作中的流式方案可提供高达 76.6% 的所需产物，纯度高达 99%。此外，反应效率也大大提高，产量为 0.49 克/小时，总反应时间从间歇式工艺的数小时明显缩短到流式工艺的数分钟。

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

Journal of Flow Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

6.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： The main focus of the journal is flow chemistry in inorganic, organic, analytical and process chemistry in the academic research as well as in applied research and development in the pharmaceutical, agrochemical, fine-chemical, petro- chemical, fragrance industry.