Synthetic method of avibactam intermediate (2S,5S)-N-protective group-5-hydroxy-2-piperidine formate

• Main Authors: YANG QINGKUN, SHI JUNSHOU, YAN LIANZHONG, WANG WENKUAN, ZHENG CHANGSHENG, LI ZHUOHUA
• Format: Patent
• Language: Chinese; English
• Published: 17.12.2019
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a synthetic method of an avibactam intermediate (2S,5S)-N-protective group-5-hydroxy-2-piperidine formate. N-protective group-L-pyroglutamate (SM) is taken as an initial raw material, and the (2S,5S)-N-protective group-5-hydroxy-2-piperidine formate is obtained through six steps of reactions including trimethyl sulfoxide iodide recarburization ring opening, halogenation under the action of acid, high-selectivity reduction, lactone ring formation under the catalysis of acid, piperidine ring closing under the action of alkali and hydrolysis. The synthetic method is mild in reaction conditions, simple and convenient to operate, easy in impurity control and stable in yield. The used reagents are low in price, the cost is effectively reduced, and the method is environment-friendly and suitable for industrial production. 本发明公开了一种阿维巴坦中间体(2S,5S)-N-保护基-5-羟基-2-甲酸哌啶的合成方法。本发明以N-保护的-L-焦谷氨酸酯(SM)为起始原料，通过三甲基碘化亚砜增碳开环，酸作用下卤代，高选择性还原，酸催化下成内酯环，在碱作用下关哌啶环，水解共6步反应得到(2S,5S)-N-保护基-5-羟基-2-甲酸哌啶。该合成方法的反应条件温和，操作简便，