Details

Autor(en) / Beteiligte

• Wang, Tao
• Du, Liang-Dong
• Wan, Ding-jian
• Li, Xiang
• Chen, Xin-Zhi
• Wu, Guo-Feng

Titel

Use of Lipase Catalytic Resolution in the Preparation of Ethyl (2S,5R)‑5-((Benzyloxy)amino)piperidine-2-carboxylate, a Key Intermediate of the β‑Lactamase Inhibitor Avibactam

Ist Teil von

• Organic process research & development, 2018-12, Vol.22 (12), p.1738-1744

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Here we describe an efficient and cost-effective chemoenzymatic synthesis of the β-lactamase inhibitor avibactam starting from commercially available ethyl 5-hydroxy­picolinate hydro­chloride. Avibactam was synthesized in 10 steps with an overall yield of 23.9%. The synthetic route features a novel lipase-catalyzed resolution step during the preparation of (2S,5S)-ethyl 5-hydroxy­piperidine-2-carboxylate, a valuable precursor of the key intermediate ethyl (2S,5R)-5-((benzyloxy)­amino)­piperidine-2-carboxylate. Our synthetic route was used to produce 400 g of avibactam sodium salt.