Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of chlorzoxazone

A technology for chlorzoxazone and oxazolone, which is applied in the field of drug synthesis, can solve the problems of enhanced nucleophilicity, high cost, difficulty in industrialized production and the like, and achieves the effects of high yield and purity, and easy operation.

Pending Publication Date: 2021-12-21
LUNAN PHARMA GROUP CORPORATION
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The first method has higher requirements on equipment, and needs to prepare chlorzoxazone with carbon monoxide under high pressure under the condition of noble metal as catalyst. The cost of this method is relatively high, and the process operation is difficult
The second method is prepared by Hofmann rearrangement reaction. Although the reaction conditions are mild, 5-chlorosalicylamide is not easy to obtain. It is limited to laboratory level research and industrial production is difficult.
[0008] The above-mentioned processes all use substituted chlorophenols to prepare chlorzoxazone. In the preparation process using urea as the cyclization reagent in Method 3, the cyclization is initially carried out in a strong acid environment, but a large amount of ammonia will be produced due to the degradation of urea in the later stage of the reaction. Gas, so that the whole reaction system is neutral to weakly alkaline, the nucleophilicity of the amino group under this system is significantly enhanced compared with the acidic environment, and the reaction is carried out at high temperature, so a small amount of polymer (crude product and Crude product, crude product and starting material, starting material and crude product, starting material and starting material), difficult to refine and remove, affecting the purity of the product

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 chlorzoxazone
  • Preparation method of chlorzoxazone
  • Preparation method of chlorzoxazone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] At room temperature, after replacing the reactor with oxygen 3 times, add 2(3H)-benzo[d]oxazolone-5-carboxylic acid (17.91g, 0.10mol), CuCl 2 (29.58g, 0.22mol), sodium hydroxide (8.80g, 0.22mol), Ag 2 CO 3 (2.76g, 0.01mol) and N,N-dimethylformamide / dimethyl sulfoxide (V:V=1:1, 400ml), the reaction system is fed with oxygen, and the temperature is controlled at 120-125°C until the end of the reaction Afterwards, the reaction solution was cooled to room temperature, filtered, added in purified water (2500ml), stirred and crystallized for 1-2h, and filtered to obtain a crude product, which was subjected to ethanol / purified water (V 乙醇 :V 纯化水 =1:3, 2700ml) system was recrystallized to obtain chlorzoxazone with a total yield of 92.2% and a purity of 99.947%.

Embodiment 2

[0042] At room temperature, after replacing the reactor with oxygen 3 times, add 2(3H)-benzo[d]oxazolone-5-carboxylic acid (17.91g, 0.10mol), CuCl 2 (18.82g, 0.14mol), sodium hydroxide (5.60g, 0.14mol), Ag 2 CO3 (2.76g, 0.01mol) and N,N-dimethylformamide (400ml), the reaction system was fed with oxygen, the temperature was controlled at 140-145°C until the reaction was completed, the reaction solution was cooled to room temperature, filtered, and purified water (2500ml), stirred and crystallized for 1-2h and then filtered to obtain the crude product, which was subjected to ethanol / purified water (V 乙醇 :V 纯化水 =1:3, 2700ml) system was recrystallized to obtain chlorzoxazone with a total yield of 90.1% and a purity of 99.891%.

Embodiment 3

[0044] At room temperature, after replacing the reactor with oxygen 3 times, add 2(3H)-benzo[d]oxazolone-5-carboxylic acid (17.91g, 0.10mol), CuCl 2 (17.48g, 0.13mol), sodium hydroxide (5.20g, 0.13mol), Ag 2 CO 3 (2.76g, 0.01mol) and dimethyl sulfoxide (400ml), the reaction system was fed with oxygen, the temperature was controlled at 145-150°C until the reaction was completed, the reaction solution was cooled to room temperature, filtered, and added to purified water (2500ml) , filtered to obtain the crude product after stirring and crystallizing for 1~2h, and the obtained crude product was subjected to ethanol / purified water (V 乙醇 :V 纯化水 =1:3, 2700ml) system was recrystallized to obtain chlorzoxazone with a total yield of 89.5% and a purity of 99.861%.

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 belongs to the technical field of drug synthesis, and provides a novel preparation method of chlorzoxazone, wherein 2 (3H)-benzo [d] oxazolione-5-carboxylic acid is used as a starting material and is subjected to decarboxylation and chlorination with CuCl2 under alkaline and Ag salt conditions to prepare chlorzoxazone, and the problems that in the prior art, polymeric impurities are easily generated and are difficult to refine and remove, and the purity of a product is influenced are solved. The product obtained by the method is high in yield and purity, and is more suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of chlorzoxazone. Background technique [0002] Chlorzoxazone (Chlorzoxazon, Chlorzoxazon), chemically called 5-chloro-2 (3H)-benzoxazolone, is a powerful oral muscle relaxant, developed by McNeil Pharmaceuticals in the United States, and Listed in the mid-1960s. Chlorzoxazone has been mass-produced in the United States and Japan, and is recorded in the 24th edition of the United States Pharmacopoeia and the 13th edition of the Japanese Pharmacopoeia. This product is one of the 100 commonly used drugs in the United States in recent years, and is listed in the "National Basic Medical Insurance Drug Catalog" and "National Non-Prescription Drug Catalog" in China. This product is a central muscle relaxant, which mainly acts on the spinal cord and the subcortical center of the cerebral cortex, inhibits the polysynaptic nerve reflex arc rel...

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): C07D263/58
CPCC07D263/58
Inventor 张乃华鲍广龙
Owner LUNAN PHARMA GROUP CORPORATION
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com