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

A kind of method of industrialized synthesis butoconazole nitrate intermediate

A kind of technology of butconazole nitrate and intermediate, applied in the field of synthesis technology of butoconazole nitrate, can solve the problems such as product yield and purity that cannot satisfy industrialized production, high cost, complicated butconazole nitrate production process and the like

Active Publication Date: 2018-01-16
ZHUZHOU QIANJIN PHARMA
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, most of the prior art studies on this drug are concentrated at the laboratory level. For the large-scale production of medicines, the production process of butoconazole nitrate provided by the prior art is complicated, the cost is high, and the product yield and purity are also low. Can not 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 synthesis butoconazole nitrate intermediate
  • A kind of method of industrialized synthesis butoconazole nitrate intermediate
  • A kind of method of industrialized synthesis butoconazole nitrate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] 1-(2-Hydroxy-4-(4-chlorophenyl)butyl)-1hydro-imidazole was prepared as follows:

[0050] (1) Get 7kg concentration of 20% sodium hydride DMF solution, under ice bath condition, add dropwise 7kg concentration of 20% imidazole DMF solution while stirring at a speed of 2ml / s, and stir and react at 60°C for 60min; After cooling in an ice-salt bath, slowly add 5 kg of 1-chloro-4-(4-chlorophenyl)-2-butanol, stir and react at 60°C for 120 minutes, and cool in an ice-salt bath to obtain a reaction solution;

[0051] (2) Get the reaction solution gained in step (1), add 25% n-hexane accounting for the weight of the reaction solution, stir at a speed of 3 rpm for 15 min, then add ice water accounting for 350% of the weight of the reaction solution, Stir at a speed of 3 revolutions per second until the precipitation stops and then filter, wash the filter cake once with water accounting for 1 / 3 times the weight of the filter cake, and dry it by centrifugation at a speed of 2825 r / m...

Embodiment 2

[0054] Compared with Example 1, the difference is only that the step (1) is specifically:

[0055] (1) Take 5 kg of a 10% sodium hydride DMF solution, add 5 kg of a 10% imidazole DMF solution dropwise while stirring at a speed of 1 ml / s under ice bath conditions, and stir and react at 58° C. for 55 min; After cooling in an ice-salt bath, slowly add 3kg of 1-chloro-4-(4-chlorophenyl)-2-butanol, stir and react at 58°C for 115min, and cool in an ice-salt bath to obtain a reaction solution.

[0056] After testing, the yield of the product of this example was 70.7%. The target product and impurity content were detected by HPLC and standard substances. After testing, the content of the target product 1-(2-hydroxyl-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole is 98.78%, 1-(1-chloro-4-(4-chlorophenyl ) butane-2-yl)-1 hydrogen-imidazole content is 0.87%, 4-(4-(1 hydrogen-imidazol-1-yl) phenyl)-1-chloro-2-butanol content is 0.09% %.

Embodiment 3

[0058] Compared with Example 1, the difference is only that the step (1) is specifically:

[0059] (1) Get 9kg concentration of 30% sodium hydride DMF solution, under ice bath conditions, add dropwise 9kg concentration of 30% imidazole DMF solution while stirring at a speed of 3ml / s, and stir and react at 62°C for 65min; After cooling in an ice-salt bath, slowly add 7kg of 1-chloro-4-(4-chlorophenyl)-2-butanol, stir and react at 62°C for 125min, and cool in an ice-salt bath to obtain a reaction solution.

[0060] After testing, the yield of the product of this example was 70.3%. The target product and impurity content were detected by HPLC and standard substances. After detection, the content of the target product 1-(2-hydroxyl-4-(4-chlorophenyl)butyl)-1 hydrogen-imidazole is 99.01%, 1-(1-chloro-4-(4-chlorophenyl )butane-2-yl)-1hydrogen-imidazole content is 0.63%, 4-(4-(1hydrogen-imidazol-1-yl)phenyl)-1-chloro-2-butanol content is 0.07% %.

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-hydroxy-4-(4-chlorphenyl)butyl)-1-hydro-imidazole. The method comprises the following steps: (1) taking a sodium hydride DMF (dimethyl formamide) solution, slowly dropwise adding an imidazole DMF solution under the condition of an ice bath and heating and stirring the solutions to react; after cooling, slowly adding 1-chloro-4-(4-chlorphenyl)-2-butanol, heating and stirring the materials to react and cooling to obtain a reaction liquid; and (2) taking the reaction liquid obtained in the step (1), mixing the reaction liquid with ice water under the condition of stirring, filtering the mixture after stopping separating out a precipitate, washing a filter cake and drying and re-crystallizing the filter cake, thus obtaining the butoconazole nitrate intermediate. In the method provided by the invention, the conditions and parameters in the synthetic process are comprehensively and preferentially selected, thus increasing the purity and yield of the product. Therefore, the method is more suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a synthesis process of butoconazole nitrate, in particular to a method for synthesizing butoconazole nitrate intermediate 1-(2-hydroxyl-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-imidaz ole nitrate, a newpotent antifungal agent", the synthesis method of butoconazole nitrate is disclosed; in recent years, scholars such as Zhang Haibo have also reported the synthesis method of this drug. [0006] The main synthetic route of butoconazole nitrate is ...

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): C07D233/60C07D233/56
CPCC07D233/56C07D233/60
Inventor 彭开锋刘逆夫文峰球伍实花龚云李伏君
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