Improved Preparation of a Key Hydroxylamine Intermediate for Relebactam: Rate Enhancement of Benzyl Ether Hydrogenolysis with DABCO,Organic Process Research & Development

当前位置： X-MOL 学术 › Org. Process Res. Dev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Improved Preparation of a Key Hydroxylamine Intermediate for Relebactam: Rate Enhancement of Benzyl Ether Hydrogenolysis with DABCO
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-02-01 00:00:00 , DOI: 10.1021/acs.oprd.7b00381
Jianguo Yin ₁ , Mark Weisel ₁ , Yining Ji ₁ , Zhijian Liu ₁ , Jinchu Liu ₁ , Debra J. Wallace ₁ , Feng Xu ₁ , Benjamin D. Sherry ₁ , Nobuyoshi Yasuda ₁

Affiliation

Previous methods to prepare a bicyclic N-hydroxyl urea intermediate in the synthesis of the potent β-lactamase inhibitor relebactam were effective, but deemed unsuitable for long-term use. Therefore, we developed an in situ protection protocol during hydrogenolysis and a robust deprotection/isolation sequence of this unstable intermediate employing a reactive crystallization. During the hydrogenation studies, we discovered a significant rate enhancement of O-benzyl ether hydrogenolysis in the presence of organic amine bases, especially DABCO. The broader utility of the application of organic bases on the hydrogenolysis of a range of O- and N-benzyl-containing substrates was demonstrated.

中文翻译：

改善雷贝巴坦关键羟胺中间体的制备：用DABCO加速苄醚氢解的速率

在有效的β-内酰胺酶抑制剂雷巴坦的合成中，制备双环N-羟基脲中间体的先前方法是有效的，但认为不适合长期使用。因此，我们开发了氢解过程中的原位保护方案，并采用反应性结晶技术对该不稳定中间体进行了稳健的脱保护/分离步骤。在氢化研究期间，我们发现在有机胺碱（尤其是DABCO）存在下，O-苄基醚氢解反应的速率显着提高。证明了在一系列含O-和N-苄基的底物进行氢解后，有机碱的应用具有更广泛的用途。

更新日期：2018-02-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11