Industrial production method of high purity loxoprofen sodium dehydrate

A technology for loxoprofen sodium dihydrate and a production method, which is applied in the field of high-purity loxoprofen sodium dihydrate to achieve the effects of shortening reaction time, improving product quality and yield, and increasing conversion rate

Inactive Publication Date: 2015-02-04
合肥远志医药科技开发有限公司
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a kind of industrial production method of high-purity loxoprofen sodium dihydrate in orde

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
  • Industrial production method of high purity loxoprofen sodium dehydrate
  • Industrial production method of high purity loxoprofen sodium dehydrate
  • Industrial production method of high purity loxoprofen sodium dehydrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] A kind of industrialized production method of high-purity loxoprofen sodium dihydrate:

[0040] (1) Preparation of compound II:

[0041] Add 2Kg of dimethyl adipate to 6Kg of toluene, stir and cool to 0-10°C to obtain a toluene solution of dimethyl adipate, and then add dropwise 28% sodium methoxide to the toluene solution of dimethyl adipate Methanol solution 2Kg, and react at 0-10°C for 1 hour under heat preservation. After the reaction, heat up to 60-80°C and concentrate under normal pressure to obtain a ring-closing product reaction solution; then cool the obtained reaction solution to 10-15 After ℃, add 3Kg N, N-dimethylformamide (DMF), then directly dropwise add 2Kg of compound 2-(4-bromomethylphenyl) propionate shown in formula I in the reaction solution, dropwise process Maintain the temperature at 10-15° C., carry out the substitution reaction, and the reaction time is 3-5 hours. After the reaction is completed (normalized detection of the compound 2-(4-bromom...

Embodiment 2

[0053] A kind of industrialized production method of high-purity loxoprofen sodium dihydrate:

[0054] (1) Preparation of Compound II:

[0055] Add 2Kg of dimethyl adipate to 6Kg of toluene, stir and cool to 0-10°C to obtain a toluene solution of dimethyl adipate, and then add dropwise 28% sodium methoxide to the toluene solution of dimethyl adipate Methanol solution 2.2Kg, and react at 0-10°C for 1 hour under heat preservation, after the reaction, heat up to 60-80°C and concentrate under normal pressure to obtain a ring-closing product reaction solution; then cool the obtained reaction solution to 10-80°C After 15°C, 3Kg N,N-dimethylformamide (DMF) was first added, and then 2.1Kg of the compound 2-(4-bromomethylphenyl) propionate shown in formula I was directly added dropwise to the reaction solution, and then Adding process maintains temperature at 10~15 ℃, carries out substitution reaction, and the reaction time is 3~5h, after reaction is finished (with HPLC area normaliza...

Embodiment 3

[0062] A kind of industrialized production method of high-purity loxoprofen sodium dihydrate:

[0063] (1) Preparation of Compound II:

[0064] Add 2Kg of dimethyl adipate to 6Kg of toluene, stir and cool to 0-10°C to obtain a toluene solution of dimethyl adipate, and then add dropwise 28% sodium methoxide to the toluene solution of dimethyl adipate Methanol solution 1.9Kg, and react at 0-10°C for 1 hour under heat preservation, after the reaction, heat up to 60-80°C and concentrate under normal pressure to obtain a ring-closing compound reaction liquid; then cool the obtained reaction liquid to 10-10°C After 15°C, 3Kg N, N-dimethylacetamide was first added, and then 2.2Kg of the compound 2-(4-bromomethylphenyl) propionate shown in formula I was directly added dropwise to the reaction solution, and the dropping process maintained Temperature is 10~15 ℃, carries out substitution reaction, and the reaction time is 3~5h, after reaction finishes (with HPLC area normalization dete...

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 an industrial production method of high purity loxoprofen sodium dehydrate; according to the method, adipic acid diester is taken as a starting material for Dieckmann condensation reaction with 2-(4-bromomethyl phenyl) propionate under strong alkaline conditions, the yield and quality of compound II are effectively improved, because the adipic acid diester on the market is lower in cost than 2-ethoxy carbonyl cyclopentanone, the production cost can be greatly reduced; the compound obtained by reaction is processed sequentially by hydrolysis and decarboxylation under acidic conditions, in the hydrolysis and decarboxylation process, generated low boiling point alcohol solvents and carbon dioxide gas can be removed by atmospheric distillation, the reaction can be effectively promoted, the reaction time is shortened, the conversion rate is improved; and finally the final product loxoprofen sodium dehydrate is generated under the condition of aqueous sodium hydroxide solution. The preparation method can greatly reduce the manufacturing cost of loxoprofen sodium, and is more suitable for the industrialized production than the existing technology.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, in particular to an industrial production method of high-purity loxoprofen sodium dihydrate. Background technique [0002] Loxoprofen sodium (Loxoprofen sodium), structural formula (TM) is as follows: [0003] [0004] Loxoprofen sodium was first developed by Japan's Sankyo Co., Ltd., and now it is the first-selling variety of non-steroidal anti-inflammatory drugs in Japan. It has been recorded by the Japanese Pharmacopoeia, and China has imported it. The chemical name is 2-[4-(2-oxocyclopentane-1-ylmethyl)phenyl]propionate sodium dihydrate, which belongs to di-arylpropionic acid non-steroidal anti-inflammatory drugs, Chinese patent CN101412670, Chinese Journal of New Drugs 2000, 9, 11 765-767, J.Med.Chem.2010, 53, 7879-7882 and many other documents have reported that 2-(4-bromomethylphenyl) propionate and Condensation of 2-ethoxycarbonyl cyclopentanone, followed by hydroly...

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
IPC IPC(8): C07C59/86C07C51/41
CPCC07C51/412C07C51/38C07C67/313C07C2601/08C07C59/86C07C69/757
Inventor 胡孟奇刘斐孙松
Owner 合肥远志医药科技开发有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap