Method for preparing azetidinone compound and intermediate of azetidinone compound

Patent metadata

Field	Value
Publication number	US-9926268-B2
Application number	US-201515317297-A
Country	US
Kind code	B2
Filing date	Jun 5, 2015
Priority date	Jun 9, 2014
Publication date	Mar 27, 2018
Grant date	Mar 27, 2018

Abstract

Disclosed is a new method for preparing an azetidinone compound represented by formula (I). The carboxylic ketoester represented by formula (II) serves as the raw material and is subjected to Grignard addition, stereoselective dehydration, ester group reduction, hydroxyl group protection, addition with imine after condensation with a chiral auxiliary, cyclization and deprotection to obtain the compound represented by formula (I). The present invention has advantages of easily available raw material, a few synthetic steps, simple operation, high yield, good stereoselectivity and low cost, and can be used for industrial production.

First claim

The invention claimed is:

1. A compound of formula V:

2. A method for preparing the compound of claim 1 , comprising: selectively reducing the ester of formula IV to the alcohol of formula V under the action of a reducing agent:

wherein R 1 is C 1 -C 6 alkyl.

3. The method according to claim 2 , wherein a solvent used in reducing the ester of formula IV to the alcohol of formula V is selected from dichloromethane, tetrahydrofuran, toluene or dioxane.

4. The method according to claim 2 , wherein the reducing agent is diisobutylaluminium hydride (DIBAH).

5. The method according to claim 2 , wherein a molar ratio of the compound of formula IV to the reducing agent is 1:2.5˜5.0.

6. The method according to claim 1 , wherein in the ester of formula IV, R 1 is methyl, ethyl or isopropyl.

7. The method according to claim 1 , wherein a solvent used in reducing the ester of formula IV to the alcohol of formula V is toluene.

8. The method according to claim 1 , wherein a molar ratio of the compound of formula IV to the reducing agent is 1:3.0˜4.0.

Assignees

• Zhejiang Hisun Pharm Co Ltd

Inventors

• Bai Hua
• Zhao Xuyang
• Zhang Yuncai
• Li Xufei
• Zhang Yong
• Xu Dezhou
• Zhang Li
• Xu Xiaojie
• Zhu Qifeng
• Wang Xiaoming
• Yang Zhiqing
• Zhong Zehua
• Zhang Jian

Classifications

• C07C67/30

  by modifying the acid moiety of the ester, such modification not being an introduction of an ester group · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07C59/56

  containing halogen · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• C07D205/08 Primary

  with one oxygen atom directly attached in position 2, e.g. beta-lactams · CPC title