公开(公告)号：EP3978505A1

公开(公告)日：2022-04-06

申请号：EP19950893.8

申请日：2019-10-28

申请人： Jilin Asymchem Pharmaceuticals Co., Ltd.

发明人： HONG, Hao ,  JAMES, Gage ,  CHEN, Chaoyong ,  LU, Jiangping ,  JIANG, Yong ,  TAO, Jian ,  LUO, Yong

IPC分类号： C07F9/6561 ,  B01J31/22

摘要： The present invention discloses a continuous preparation method for a penem intermediate MAP. The continuous preparation method includes the following steps: step S1, in a column-type continuous reactor, using a rhodium-loaded catalyst to catalyze 4-nitrobenzyl(R) -2-diazo-4-((2R,3S)-3-((R)-1-hydroxyethyl)-4-oxoazetidin-2-yl)-3-oxopentanoate to generate a cyclization reaction so as to form a first intermediate, herein the rhodium-loaded catalyst is loaded in the column-type continuous reactor, and the rhodium-loaded catalyst has the following structural formula: (P-COO)- x Rh 2 (OOCR 1 ) 4-x ; step S2, performing an esterification reaction on the first intermediate, a diphenyl chlorophosphate and a diisopropylethylamine in a second continuous reactor, to obtain a product system containing the penem intermediate MAP; and step S3, performing crystallization treatment on the product system, to obtain the penem intermediate MAP. The column-type continuous reactor and the rhodium-loaded catalyst enable the cyclization reaction to perform efficiently at a lower temperature, thereby the energy consumption is reduced