Method for preparing (S)-ornidazole

A technology of levo-ornidazole and nitroimidazole, which is applied in the field of preparation of levo-ornidazole, can solve the problems of low yield, long reaction steps, and high cost of ornidazole optical enantiomers, and achieve high yield, The effect of mild reaction conditions and simple operation

Inactive Publication Date: 2010-09-01
HC SYNTHETIC PHARMA CO LTD
View PDF4 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

One is splitting by enzymatic method, see Chinese patent CN400312A, the cost required by this method to obtain the optical enantiomer of ornidazole is relatively large, and it is not suitable for large-scale production; the other method is disclosed in Chinese patent 200510127033.3, this reaction The process is simple, the reaction steps are few, and the disadvantage is that there are many side reactions of chiral oxirane, and the yield is low; another method is disclosed in Chinese patent 200710018857.6, and the reaction yield is higher, but the reaction steps are longer

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
  • Method for preparing (S)-ornidazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Embodiment 1: the preparation of L-ornidazole

[0016] Add 20L of ethyl acetate and 2kg of 2-methyl-5-nitroimidazole into a 50L reaction kettle, cool down to -10°C, and slowly add boron trifluoride in ethyl acetate solution (containing boron trifluoride about 1.1kg) (control temperature not exceeding 15°C), after the dropwise addition, slowly add 2.2LS-(+)-epichlorohydrin (control temperature not exceeding 15°C), and react at 10°C for 5 hours after dropping Slowly add the reaction solution into 18kg of ice-water mixture, and stir the reaction for 5 hours at a temperature not exceeding 30°C. Adjust the pH value to about 1.0 with concentrated hydrochloric acid, remove the organic layer, adjust the pH value of the aqueous layer to 7.0 with concentrated ammonia water, stir and crystallize for 24 hour, filter, wash with water, and dry to obtain L-ornidazole 3.21kg. Melting point: 91.5°C-92.5°C[a] D 20 =-68.3 (C=1.0, dichloromethane), purity 99.82%.

Embodiment 2

[0017] Embodiment 2: the preparation of L-ornidazole

[0018] Add 20L of ether and 2kg of 2-methyl-5-nitroimidazole into a 50L reaction kettle, cool down to -15°C, and slowly add a solution of boron trifluoride in ether (containing about 1.1kg of boron trifluoride) ( Control the temperature not to exceed 15°C), after the dropwise addition, slowly add 2.3LS-(+)-epichlorohydrin (control the temperature not to exceed 15°C), and react at 5°C for 5 hours after the dropwise addition, slowly dissolve the reaction solution Add 18kg of ice-water mixture, stir and react at a temperature not exceeding 30°C for 5 hours, adjust the pH value to about 1.5 with concentrated hydrochloric acid, separate the organic layer, adjust the pH value of the aqueous layer to 7.5 with 20% sodium carbonate, stir and crystallize for 24 hours, Filter, wash with water, and dry to obtain 3.13 kg of L-ornidazole. Melting point: 91.0°C-92.5°C[a] D 20 =-68.4 (C=1.0, dichloromethane), purity 99.72%.

Embodiment 3

[0019] Embodiment 3: the preparation of L-ornidazole

[0020] Add 20L of ether and 2kg of 2-methyl-5-nitroimidazole into a 50L reactor, cool down to -15°C, and slowly add boron trifluoride in acetone solution (containing about 1.1 kg of boron trifluoride) ( Control the temperature not to exceed 15°C), after the dropwise addition, slowly add 2.35L S-(+)-epichlorohydrin (control the temperature not to exceed 15°C), and react at 5°C for 4 hours after the dropwise addition, the reaction solution was slowly Slowly add 18kg of ice-water mixture, the temperature does not exceed 30°C and stir for 5 hours, adjust the pH value to about 2 with concentrated hydrochloric acid, separate the organic layer, adjust the pH value of the water layer to 7.0 with 20% sodium hydroxide, stir and crystallize After 18 hours, filter, wash with water, and dry to obtain 3.13 kg of L-ornidazole. 92.0℃-93.0℃[a] D 20 =-68.6 (C=1.0, dichloromethane), purity 99.91%.

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
optical purityaaaaaaaaaa
Login to view more

Abstract

The invention provides a method for preparing (S)-ornidazole. The method comprises the following steps of: adding an organic solvent and 2-methyl-5-ornidazole, slowly adding a catalyst dropwise with stirring first, then slowly dripping S-(+)-epichlorohydrin into the mixed solution, and after the S-(+)-epichlorohydrin is dripped completely, performing a reaction for 2 to 10 hours at the temperature of between 0 and 20 DEG C; slowly adding the reaction solution into the ice-water mixture, stirring the mixed solution for a reaction for 10 minutes and 5 hours at the temperature of no less than 30 DEG C, adjusting a pH value of the mixed solution to 1.0 to 2.0 with acid, removing an organic layer, adjusting the pH value of a water layer to 6.0 to 8.0 with alkali, stirring the mixed solution for 1 to 24 hours for crystallization, filtering the reaction solution, washing the product obtained by water, and drying the product to obtain the (S)-ornidazole. The method has the advantages of high product purity, simplified procedures and the suitability for industrial production.

Description

Technical field: [0001] The invention relates to a preparation method of L-ornidazole. technical background: [0002] Ornidazole is ((+)) 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (Ornidazole, CAS16773-42-5). Ornidazole is a nitroimidazole derivative, which is a powerful drug against anaerobic bacteria and antiprotozoal infection. Broader third-generation nitroimidazole derivatives. The antimicrobial effect of ornidazole is through the reduction of the nitro group in its molecule to an amino group in an oxygen-free environment, or through the formation of free radicals to interact with cellular components, resulting in the death of microorganisms. There are three methods for preparing the counterpart of L-ornidazole in the prior art. One is splitting by enzymatic method, see Chinese patent CN400312A, the cost required by this method to obtain the optical enantiomer of ornidazole is relatively large, and it is not suitable for large-scale production; the other...

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 Applications(China)
IPC IPC(8): C07D233/94
Inventor 杨成
Owner HC SYNTHETIC PHARMA CO LTD
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