Stereoinvertive Deoxyamination of trans-2-Aminocyclohexanol Using Bose–Mitsunobu Azidation and Staudinger Reaction for the Stereoselective Synthesis of Edoxaban

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2023-08-01 DOI:10.1021/acs.oprd.3c00189

Hidenori Ochiai*, Shunichi Kubota, Miwa Sasagawa, Taiki Mihara, Atsuhiro Yamashita, Tomohide Nakamata and Akira Nishiyama,

引用次数: 0

Abstract

Stereoinvertive deoxyamination involving Bose–Mitsunobu azidation and the Staudinger reaction, which proceeds under mild conditions in the presence of a neighboring group, was successfully applied for the synthesis of edoxaban. The one-pot process allowed access to key intermediates of edoxaban without isolating azide intermediates. Furthermore, the efficiency of the Bose–Mitsunobu azidation was dramatically improved by changing the substituent on the neighboring group from the Boc group to a thiazole carbonyl unit.

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用Bose-Mitsunobu叠氮化和Staudinger反应立体选择性合成乙多沙班的反式-2-氨基环己醇立体可逆脱氧胺化

利用Bose-Mitsunobu叠氮化和Staudinger反应的立体可逆脱氧胺反应，在邻基存在的温和条件下成功地合成了依多沙班。一锅工艺允许在不分离叠氮中间体的情况下获得依多沙班的关键中间体。此外，通过将邻基上的Boc取代基改为噻唑羰基，可以显著提高Bose-Mitsunobu叠氮化反应的效率。

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.