Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of method of industrialized production butoconazole nitrate intermediate

A technology for butoconazole nitrate and intermediates, which is applied in the field of industrial production of butoconazole nitrate intermediates, can solve the problems that the product yield and purity cannot meet industrial production, high cost, complex production process of butoconazole nitrate, etc.

Active Publication Date: 2018-03-23
ZHUZHOU QIANJIN PHARMA
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, most of the research on the drug in the prior art is concentrated at the laboratory level. For the large-scale production of the drug, the production process of butoconazole nitrate provided by the prior art is complicated, the cost is high, and the product yield and purity cannot be achieved. Meet the needs of industrial production

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
  • A kind of method of industrialized production butoconazole nitrate intermediate
  • A kind of method of industrialized production butoconazole nitrate intermediate
  • A kind of method of industrialized production butoconazole nitrate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] 1-(2-Chloro-4-(4-chlorophenyl)butyl)-1hydro-imidazole was prepared according to the following procedure:

[0052] (1) Take 3kg of 1-(2-hydroxy-4-(4-chlorophenyl)butyl)-1hydro-imidazole, fully dissolve it in 30kg of dichloromethane, and drop it at a rate of 1.5ml / s at 20°C Add 3.5kg of thionyl chloride, slowly raise the temperature to 33°C, keep it warm for 1 hour, then reflux at 60°C for 1 hour, and slowly cool down to below 15°C to obtain a reaction solution;

[0053] (2) Add water at 10°C at a rate of 0.5ml / s to the reaction solution obtained in step (1) while stirring, the volume ratio of the reaction solution to water is 0.005:1, and then add water at a rate of 1.0 to 1.5kg / L Add anhydrous sodium carbonate, filter with suction, discard the solid, concentrate the liquid at 55°C until no dichloromethane evaporates, and dry to obtain the obtained product.

[0054] After testing, the yield of the product in this example was 99.18%. The target product and impurity cont...

Embodiment 2

[0056] Compared with Example 1, the difference is only that the step (1) is specifically:

[0057] (1) Take 2kg of 1-(2-hydroxy-4-(4-chlorophenyl)butyl)-1hydro-imidazole, fully dissolve it in 25kg of dichloromethane, and add 2kg of it dropwise at a rate of 1ml / s at 15°C For thionyl chloride, slowly raise the temperature to 30°C, keep it warm for 0.5 hours, then reflux at 55°C for 0.5 hours, and slowly cool to 10°C to obtain a reaction solution.

[0058] After testing, the yield of the product in this example was 97.32%. The target product and impurity content were detected by HPLC and standard substances. After testing, the content of the target product 1-(2-chloro-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole is 98.93%, 1-(1-chloro-4-(4-chlorophenyl The content of )butane-2-yl)-1 hydrogen-imidazole is 0.57%, and the content of 1-(2-hydroxy-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole is 0.25%.

Embodiment 3

[0060] Compared with Example 1, the difference is only that the step (1) is specifically:

[0061] (1) Take 5 kg of 1-(2-hydroxy-4-(4-chlorophenyl) butyl)-1 hydrogen-imidazole, fully dissolve it in 35 kg of dichloromethane, and add 5 kg of it dropwise at a rate of 2 ml / s at 25°C Thionyl chloride was slowly heated to 35°C, kept for 1.5 hours, then refluxed at 65°C for 1.5 hours, and slowly cooled to 20°C to obtain a reaction solution.

[0062] After testing, the yield of the product of this example was 98.14%. The target product and impurity content were detected by HPLC and standard substances. After testing, the content of the target product 1-(2-chloro-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole is 98.97%, 1-(1-chloro-4-(4-chlorophenyl )butane-2-yl)-1H-imidazole content was 0.58%, and 1-(2-hydroxy-4-(4-chlorophenyl)butyl)-1H-imidazole content was 0.22%.

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 relates to a method for industrially producing a butoconazole nitrate intermediate 1-(2-chlorine-4-(4-chlorphenyl) butyl)-1hydrogen-imidazole. The method comprises steps as follows: (1), 2-5 parts of 1-(2-hydroxyl-4-(4-chlorphenyl) butyl)-1hydrogen-imidazole is taken and sufficiently dissolved in 20-40 parts of dichloromethane, 2-5 parts of thionyl chloride are slowly and dropwise added at the temperature of 15 DEG C-25 DEG C, the mixture is slowly heated to 25 DEG C-65 DEG C for a sufficient reaction and cooled, and a reaction liquid is obtained; (2), cold water and anhydrous sodium carbonate are sequentially and slowly added to the reaction liquid obtained in the step (1), suction filtration is performed, solids are abandoned, a liquid is concentrated and dried, and the butoconazole nitrate intermediate is obtained. According to the provided method, conditions and parameters in the synthesis process are comprehensively and preferentially selected, the purity and the yield of products are improved, and the method is more suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a production process of butoconazole nitrate, in particular to a production method of butoconazole nitrate intermediate 1-(2-chloro-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole. Background technique [0002] Butoconazole nitrate is a clinically used drug for the treatment of vulvovaginal candida. It has the characteristics of significant curative effect, low recurrence rate, good tolerance, and low incidence of adverse reactions. [0003] The chemical structure of butoconazole nitrate is as follows: [0004] [0005] Keith A.M.Walker, Allen C.Braemer and others published the article in 1978 "1-[4-(4-Chlorophenyl)-2-(2,6-dichlorophenylthio)-n-butyl]-1H-imidazole nitrate, a newpotent antifungal agent ", disclosed the synthesis method of butoconazole nitrate; in recent years, scholars such as Zhang Haibo have also reported the synthesis method of the drug. [0006] The main synthetic route of butoconazole nitrate is as follo...

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): C07D233/56
CPCC07D233/56
Inventor 彭开锋张英帅文峰球李三新龚云李伏君
Owner ZHUZHOU QIANJIN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com