Lipase Catalyzed Regioselective Lactamization as a Key Step in the Synthesis of N-Boc (2R)-1,4-Oxazepane-2-Carboxylic Acid

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• 作者：Carl-Johan Aurell ; Staffan Karlsson ; Fritiof Pont茅n ; S酶ren M. Andersen
• 刊名：Organic Process Research & Development
• 出版年：2014
• 出版时间：September 19, 2014
• 年：2014
• 卷：18
• 期：9
• 页码：1116-1119
• 全文大小：218K
• ISSN：1520-586X

文摘

A synthesis of N-Boc (2R)-1,4-oxazepane-2-carboxylic acid 1 has been developed in 39% yield over seven steps starting from methyl (2R)-glycidate 2. The key step was a lipase-catalyzed regioselective lactamization of amino diester 5 into seven-membered lactam 6. The transformation was performed using SpinChem rotating flow cell technology which simplified the work up and the recycling of the enzyme. Subsequent N-Boc protection followed by chemoselective borane reduction of the lactam moiety afforded 4-tert-butyl 2-methyl (2R)-1,4-oxazepane-2,4-dicarboxylate 8. Finally, hydrolysis mediated by LiBr/Et₃N in wet acetonitrile yielded the title compound (2R)-4-(tert-butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid 1.