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

Purification method of condensation reaction intermediate in loxoprofen sodium synthesis process

A loxoprofen sodium, condensation reaction technology, applied in chemical instruments and methods, preparation of organic compounds, organic chemistry and other directions, can solve problems such as difficult separation of main products and by-products, and achieve good market application prospects and reaction conditions. Mild, low production cost effect

Active Publication Date: 2020-10-20
HUBEI XUNDA PHARMA
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Aiming at the problem that the main product and by-products in the first synthetic route of loxoprofen sodium are difficult to separate, the invention provides a purification method for the condensation reaction intermediate in the synthesis process of loxoprofen sodium, so as to improve the final product loxoprofen Quality of Profen Sodium

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
  • Purification method of condensation reaction intermediate in loxoprofen sodium synthesis process
  • Purification method of condensation reaction intermediate in loxoprofen sodium synthesis process
  • Purification method of condensation reaction intermediate in loxoprofen sodium synthesis process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] 2kg containing main product 2-[4'-(2"-oxo-1"-methoxycarbonylcyclopentyl) methyl] phenylpropanoic acid methyl ester and by-product 2-(4'-(1"- The condensation reaction product of methyl)methoxycarbonylethyl)benzyloxy-1-cyclopentene-1-carboxylate was dissolved in 1L of butanone, added 0.1kg of HZSM-5 molecular sieve, and treated at 80°C 1.5h. After the reaction is finished, filter while hot, reclaim HZSM-5 molecular sieve, and the organic solvent butanone is recovered by distillation under reduced pressure. Through chromatographic detection, the by-product 2-(4'-(1"-methyl) in the condensation reaction product Methoxycarbonylethyl)benzyloxy-1-cyclopentene-1-carboxylic acid methyl ester was completely removed.

[0027] figure 1 is the liquid chromatogram of the condensation reaction product without purification treatment, figure 2 It is the liquid chromatogram of the condensation reaction product after the purification treatment in this embodiment. In the figure, the ab...

Embodiment 2

[0029] 2kg containing main product 2-[4'-(2"-oxo-1"-methoxycarbonylcyclopentyl) methyl] phenylpropanoic acid methyl ester and by-product 2-(4'-(1"- The condensation reactant of methyl)methoxycarbonylethyl)benzyloxy-1-cyclopentene-1-formic acid methyl ester was dissolved in 4L of acetone, added 0.5kg of HZSM-5 molecular sieve, and treated at 57°C for 2.0 h. Filtrate while hot after the reaction is over, reclaim HZSM-5 molecular sieve, organic solvent acetone reclaims by vacuum distillation. Through chromatographic detection, the by-product 2-(4'-(1 "-methyl) methoxyl in the condensation reactant Carbonylethyl)benzyloxy-1-cyclopentene-1-carboxylic acid methyl ester was completely removed.

Embodiment 3

[0031] 2kg containing main product 2-[4'-(2"-oxo-1"-methoxycarbonylcyclopentyl) methyl] phenylpropanoic acid methyl ester and by-product 2-(4'-(1"- The condensation reaction product of methyl)methoxycarbonylethyl)benzyloxy-1-cyclopentene-1-carboxylate was dissolved in 20L of tetrahydrofuran, added 0.25kg of HZSM-5 molecular sieve, and treated at 66°C for 5h After the reaction is finished, filter while it is hot, reclaim HZSM-5 molecular sieve, and organic solvent tetrahydrofuran is recovered by distillation under reduced pressure. After chromatographic detection, the by-product 2-(4'-(1"-methyl)methoxycarbonyl in the condensation reaction product Ethyl)benzyloxy-1-cyclopentene-1-carboxylic acid methyl ester was removed.

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 discloses a method for purifying losoprofen sodium by concentrating reaction intermediate in synthesis process, which comprises the following steps: firstly, condensation reagents containing main product 2-(4'-(2''-oxo1''-alkoxycarbonyl cyclopentyl)methyl)phenylpropionate and by-product 2-(4'-(1''-methyl)alkoxycarbonyl ethyl)benzyloxy-1-cyclopentene-formate are dissolved in an organic solvent; and secondly, HZSM-5 molecular sieve is added for enabling the by-product to be decomposed and absorbed under the existence of the HZSM-5 molecular sieve. During the purification, the by-product 2-(4'-(1''-methyl)alkoxycarbonyl ethyl)benzyloxy-1-cyclopentene-formate is decomposed and absorbed by the HZSM-5 molecular sieve and the main product 2-(4'-(2''-oxo1''-alkoxycarbonyl cyclopentyl)methyl)phenylpropionate is purified. The method provided by the invention is simple in engineering, mild in reaction condition, less in pollution caused by three wastes, high in reaction efficiency,low in production cost and good in market application prospects.

Description

technical field [0001] The invention belongs to the field of preparation technology of loxoprofen sodium, and relates to a method for purifying a condensation reaction intermediate in the synthesis technology of loxoprofen sodium. Background technique [0002] Loxoprofen sodium is a phenylpropionic acid non-steroidal anti-inflammatory drug (NSAIDs), which was first developed by Sankyo Co., Ltd. in Japan and was launched in Japan in July 1986. The best-selling variety. The synthetic route of loxoprofen sodium is divided into with 2-(4 '-halomethyl) phenylpropionic acid (ester) as key intermediate and with 2-benzyl cyclopentanone as starting raw material two major classes, wherein The reaction conditions of the second route are harsh and the yield is low, so the current industrial production mainly adopts the first route. The condensation reaction of the intermediate 2-(4'-bromomethyl)phenyl propionate and 2-alkoxycarbonyl cyclopentanone in the first type of route easily pro...

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 Patents(China)
IPC IPC(8): C07C67/56C07C69/757
CPCC07C67/56C07C2601/10C07C69/757
Inventor 杜治平文武强李亮赵寅虎张巨寿丁一刚邓伏礼龙秉文查树义
Owner HUBEI XUNDA PHARMA