{"title":"Facile Generation of tert-Butoxycarbonyl Chloride Equivalent and Its Use in Microflow Reactor","authors":"Kana Miyamoto, Ren Okabe and Shinichiro Fuse*, ","doi":"10.1021/acs.oprd.4c00009","DOIUrl":null,"url":null,"abstract":"<p ><i>tert</i>-Butyl carbamates, carbonates, and carbonothioates are useful as bioactive compounds, functional polymers, and synthetic intermediates for a variety of valuable organic compounds. The most conventional approach for the preparation of these <i>tert</i>-butoxycarbonyl (Boc)-containing compounds includes a nucleophilic acyl substitution reaction using commercially available and stable di-<i>tert</i>-butyl dicarbonate (Boc<sub>2</sub>O). However, this method usually requires a long reaction time and high-temperature conditions because of the mild electrophilicity of Boc<sub>2</sub>O. The use of highly electrophilic BocCl and its equivalent (BocX) allows the rapid and mild preparation of Boc-containing compounds. However, BocX is unstable, which has hampered its use. Herein, we report a rapid, mild, and facile preparation of BocX from triphosgene, <i>t</i>-BuOH, and two different types of bases, <i>N</i>-methylmorpholine and <i>N</i>-methylimidazole in a microflow reactor. The <i>in situ</i>-generated BocX was immediately used for the formation of carbamates, carbonates, and a carbonothioate. The role of the two different bases was also investigated. The developed approach showed a significantly better performance than that using Boc<sub>2</sub>O.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00009","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
tert-Butyl carbamates, carbonates, and carbonothioates are useful as bioactive compounds, functional polymers, and synthetic intermediates for a variety of valuable organic compounds. The most conventional approach for the preparation of these tert-butoxycarbonyl (Boc)-containing compounds includes a nucleophilic acyl substitution reaction using commercially available and stable di-tert-butyl dicarbonate (Boc2O). However, this method usually requires a long reaction time and high-temperature conditions because of the mild electrophilicity of Boc2O. The use of highly electrophilic BocCl and its equivalent (BocX) allows the rapid and mild preparation of Boc-containing compounds. However, BocX is unstable, which has hampered its use. Herein, we report a rapid, mild, and facile preparation of BocX from triphosgene, t-BuOH, and two different types of bases, N-methylmorpholine and N-methylimidazole in a microflow reactor. The in situ-generated BocX was immediately used for the formation of carbamates, carbonates, and a carbonothioate. The role of the two different bases was also investigated. The developed approach showed a significantly better performance than that using Boc2O.
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.