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

Preparation method of montelukast

A mercaptomethyl and compound technology, applied in the field of medicine, can solve the problems of difficult recycling, potential safety hazards, and high equipment requirements, and achieve the effects of easy recycling, easy separation and purification, and low equipment requirements.

Active Publication Date: 2016-05-04
山东安信制药有限公司
View PDF6 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In the above-mentioned methods, there are high requirements on equipment or potential safety hazards, and a large amount of organic solvents are used in the whole synthesis preparation and product purification, and it is difficult to recycle them.

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
  • Preparation method of montelukast
  • Preparation method of montelukast
  • Preparation method of montelukast

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] (1) Add 11g (0.275mol) sodium hydroxide into 60ml purified water, stir and cool to 0-10℃, add 16.0g (0.11mol) of 1-(mercaptomethyl)-cyclopropylacetic acid, stir and react for 3h, get 1 -(Mercaptomethyl)-cyclopropylacetic acid dianion disodium solution;

[0036] (2) Add 50g (0.11mol) of quinolinediol compounds into 500ml of purified water, add 5.7g (0.14mol) of sodium hydroxide and 1.8g (0.0055mol) of tetrabutylammonium bromide at a temperature of 10-30℃. Stir for 0.5h, add 23g (0.12mol) p-toluenesulfonyl chloride and react for 2h after cooling to 0-5℃;

[0037] (3) The temperature of the solution in step (2) is controlled to 0-5°C and the disodium 1-(mercaptomethyl)cyclopropylacetic acid dianion solution is added within 1 hour to continue the reaction for 10 hours to obtain an aqueous solution of montelukast;

[0038] (4) Raise the temperature to 10-20℃, extract the impurities with ethyl acetate 150ml*3 3 times, adjust the pH of the water phase = 8-9 with 50% acetic acid, ext...

Embodiment 2

[0042] (1) Add 12g (0.30mol) of sodium hydroxide to 62ml of purified water, stir and cool to 0-10℃, add 16.0g (0.11mol) of 1-(mercaptomethyl)-cyclopropylacetic acid, stir and react for 3h, get 1 -(Mercaptomethyl)-cyclopropylacetic acid dianion disodium solution;

[0043] (2) Add 50g (0.11mol) of quinolinediol compounds into 500ml of purified water, add 5.7g (0.14mol) of sodium hydroxide and 1.8g (0.0055mol) of tetrabutylammonium bromide at a temperature of 10-30℃. Stir for 0.5h, add 23g (0.12mol) p-toluenesulfonyl chloride and react for 2h after cooling to 0-5℃;

[0044] (3) Control the temperature of the solution in step (2) to 5-10°C and add 1-(mercaptomethyl)cyclopropylacetic acid dianion disodium solution within 1 hour to continue the reaction for 10 hours to obtain an aqueous solution of montelukast;

[0045] (4) Raise the temperature to 10-20℃, extract the impurities with ethyl acetate 150ml*3 3 times, adjust the pH=8-8.5 with 50% acetic acid in the water phase, extract the im...

Embodiment 3

[0047] (1) Add 10g (0.25mol) of sodium hydroxide to 58ml of purified water, stir and cool to 0-10℃, add 16.0g (0.11mol) of 1-(mercaptomethyl)-cyclopropylacetic acid, stir and react for 3h to obtain 1-(Mercaptomethyl)-cyclopropylacetic acid dianion disodium solution;

[0048] (2) Add 50g (0.11mol) of quinolinediol compounds to 500ml of purified water, add 7.8g (0.14mol) of potassium hydroxide and 1.8g (0.0055mol) of tetrabutylammonium bromide at a temperature of 10-30℃ Stir for 0.5h, add 23g (0.12mol) p-toluenesulfonyl chloride and react for 2h after cooling to 0-5℃;

[0049] (3) The temperature of the solution in step (2) is controlled to 0-5°C, and 1-(mercaptomethyl)cyclopropylacetic acid dianion disodium solution is added within 1h and the reaction is continued for 10h to obtain an aqueous solution of montelukast;

[0050] (4) Raise the temperature to 10-20℃, extract the impurities with ethyl acetate 150ml*3 3 times, adjust the pH=8-9 with 50% acetic acid in the water phase, extra...

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 preparation method of montelukast. An inorganic base solution is cooled to 0-10 DEG C, 1-(mercaptomethyl)-cyclopropaneacetic acid is added, and a stirred reaction is performed to obtain a 1-(mercaptomethyl)-cyclopropaneacetic acid dianion base solution; a quinolinediol compound is dissolved into water, and inorganic base and a phase transfer catalyst are added for stirring and even mixing; after the mixture is cooled to 0-10 DEG C, paratoluensulfonyl chloride is added for a reaction to obtain a tosylate compound solution, and then the tosylate compound solution is added into the 1-(mercaptomethyl)-cyclopropaneacetic acid dianion base solution for a stirred reaction to obtain a water solution of montelukast; then the montelukast solid is obtained through post-treatment. The method is simple in technology, mild in reaction condition, economical, environmentally friendly and high in yield and makes industrialized production easy.

Description

Technical field [0001] The invention relates to a method for preparing montelukast, which belongs to the technical field of medicine. Background technique [0002] Montelukast Sodium (trade name: Shun Erning) was developed by Merck in the United States. It was first listed in Finland and Mexico in February 1998. In 1999, it was approved by the State Food and Drug Administration of China to be officially listed. Montelukast sodium is an oral leukotriene receptor antagonist, which can specifically inhibit the cysteinyl leukotriene receptors in the airway, thereby improving airway inflammation and effectively controlling asthma symptoms. In addition, it is also suitable For the treatment of allergic rhinitis. [0003] Montelukast sodium, chemical name: (+)-1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)-vinyl] Phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]sulfur]methyl]cyclopropane acetic acid monosodium salt, molecular formula: C 35 H 35 ClNNaO 3 S, molecular weight: 608.18, s...

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): C07D215/18
CPCC07D215/18
Inventor 周先国杨庆坤吴柯张兆珍董廷华高大龙江海平周学文杨波勇
Owner 山东安信制药有限公司