Synthesis of 2,3,4,5-Tetrahydro-1,5-benzoxazepine Derivatives <i>via</i> Alkoxy Migration Induced by N–O Bond Cleavage of <i>N</i>-Aryl Isoxazolidines

2,3,4,5-Tetrahydro-1,5-benzoxazepine derivatives constitute an important class of heterocycles frequently found in pharmaceuticals. In this study, we developed an efficient and practical synthetic method for the construction of 2,3,4,5-tetrahydro-1,5-benzoxazepine cores starting from N-aryl isoxazolidines. The key step involves Lewis acid–mediated alkoxy migration induced by N–O bond cleavage using aluminum chloride, providing the desired heterocyclic scaffolds in good yields. This method offers a new route to access 2,3,4,5-tetrahydro-1,5-benzoxazepine frameworks and expands the utility of N-aryl isoxazolidines in heterocycle synthesis.

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Publication Details

Journal
Chemical and Pharmaceutical Bulletin
Published
2026-06-18
DOI
https://doi.org/10.1248/cpb.c26-00150
Primary Topic
Synthesis and pharmacology of benzodiazepine derivatives
Type
article
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article

Synthesis of 2,3,4,5-Tetrahydro-1,5-benzoxazepine Derivatives via Alkoxy Migration Induced by N–O Bond Cleavage of N-Aryl Isoxazolidines

Yoshimitsu Hashimoto, Hitomi Chiaki, 田村修, Nobuyoshi Morita et al.
Chemical and Pharmaceutical Bulletin
Synthesis and pharmacology of benzodiazepine derivatives
article

Synthesis of 2,3,4,5-Tetrahydro-1,5-benzoxazepine Derivatives via Alkoxy Migration Induced by N–O Bond Cleavage of N-Aryl Isoxazolidines

Yoshimitsu Hashimoto, Hitomi Chiaki, 田村修, Nobuyoshi Morita, Kosaku Tanaka III, Motoko Nishidate
article en

Abstract

2,3,4,5-Tetrahydro-1,5-benzoxazepine derivatives constitute an important class of heterocycles frequently found in pharmaceuticals. In this study, we developed an efficient and practical synthetic method for the construction of 2,3,4,5-tetrahydro-1,5-benzoxazepine cores starting from N-aryl isoxazolidines. The key step involves Lewis acid–mediated alkoxy migration induced by N–O bond cleavage using aluminum chloride, providing the desired heterocyclic scaffolds in good yields. This method offers a new route to access 2,3,4,5-tetrahydro-1,5-benzoxazepine frameworks and expands the utility of N-aryl isoxazolidines in heterocycle synthesis.

Chemical and Pharmaceutical BulletinVol. 74(6)
Hokkaido University (JP), Showa Pharmaceutical University (JP)
Openalex Percentile: Top 11%
Synthesis and pharmacology of benzodiazepine derivatives
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