Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for controlling rearrangement ester in ibuprofen preparation process

A preparation process, the technology of ibuprofen sodium, applied in the field of medicinal chemistry, can solve the problems that the residue does not meet the requirements of drug review and is difficult to completely remove, and achieves the effect of good effect and simple operation

Inactive Publication Date: 2019-12-20
SHANDONG XINHUA PHARMA CO LTD
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The intermediate rearranged ester in this method has a residual content of 120ppm in the intermediate ibuprofen sodium salt in the next process. This process is difficult to completely remove the impurity rearranged ester in the ibuprofen process, and its residue does not meet the current drug review requirements.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for controlling rearrangement ester in ibuprofen preparation process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Add 8000ml of 1000g ibuprofen sodium salt (III), add 2g sodium hydroxide to reflux, decolorize with 50g activated carbon, filter, wash with water, acidify to pH2 with hydrochloric acid, filter to obtain ibuprofen crude product. Detection of residual rearranged esters was not detected.

Embodiment 2

[0013] Add 8000ml of 1000g ibuprofen sodium salt (III), add 20g sodium hydroxide to reflux, decolorize with 50g gac, filter, wash with water, acidify to pH2 with hydrochloric acid, filter to obtain ibuprofen crude product. Detection of residual rearranged esters was not detected.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a method for controlling rearrangement ester (II) in an ibuprofen preparation process. The method is characterized in that in the ibuprofen (I) preparation process, water is added to ibuprofen sodium salt (III), sodium hydroxide is added for reflux, activated carbon is added for decoloring, filtering and washing with water are carried out, acidifying with hydrochloric acid is carried out, and filtering is carried out. According to the method, the impurity rearrangement ester is controlled simply and conveniently, no residual rearrangement ester is found out in the ibuprofen crude product (the detection limit is 1.6 ppm), and the severe requirement of drug review for the limit of suspected genotoxic substances is met.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to the control of impurity rearrangement ester (II, α-methyl-4-(2-methylpropyl)phenylacetic acid-3-chloro-2,2- dimethyl propyl ester) method. Background technique [0002] In "The technology of preparing ibuprofen by molecular rearrangement under catalysis (CN1031939C, Xiao Wenkai)", a kind of preparation method of ibuprofen is provided, but an intermediate α-methyl-4-(2- Methylpropyl) phenylacetic acid-3-chloro-2,2-dimethylpropyl ester, referred to as rearrangement ester (II), rearrangement ester as a chlorinated product is a suspected genotoxic impurity, and its residue needs to be Fen finished products are strictly controlled. The intermediate rearrangement ester in this method has a residual content of 120ppm in the intermediate ibuprofen sodium salt in the next process. This process is difficult to completely remove the rearrangement ester of impurities in the ibuprofen proces...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C57/30C07C51/41
CPCC07C51/09C07C51/412C07C57/30
Inventor 吴辉翟吉胜赵春燕刘胜高窦国华郭统山于磊石军
Owner SHANDONG XINHUA PHARMA CO LTD