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

Preparation method of voriconazole intermediate raceme

A technology of racemate and voriconazole, which is applied in the field of preparation of voriconazole intermediate racemate, can solve the problems of low product yield, large amino genotoxic impurities, and increased production costs, and achieve product yield and quality improvement, Moderate and controllable reaction conditions, saving production time and cost

Pending Publication Date: 2022-02-18
SHAANXI LICAI GROUP XIANYANG LICAI MEDICAL
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Existing racemate 2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazol-1-yl) There are many by-products in the preparation process of -2-butanol, especially large amino genotoxic impurities are produced, the product yield is low, and the production cost is increased.

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 voriconazole intermediate raceme
  • Preparation method of voriconazole intermediate raceme

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0020] A kind of preparation method of voriconazole intermediate racemate, this method comprises the following steps:

[0021] Step 1, 3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1- Base)-2-butanol is added in the solvent and stirred and dissolved until clear;

[0022] Step 2. Add palladium carbon, formate, and organic acid respectively at room temperature, replace with nitrogen three times, raise the temperature to 40-80°C and react for 1-7.5 hours, then cool down the reaction system to room temperature;

[0023] Step 3: Filter the product obtained in Step 2, wash the filter cake with methanol, suction filter to dryness, concentrate the filtrate under reduced pressure, add purified water, stir to form a white suspension, adjust the pH to 9-12 with aqueous sodium hydroxide solution, and beat 3h, suction filtration, the filter cake was washed with purified water until neutral;

[0024] The filter cake obtained in step 4 and step 3 is dried ...

Embodiment 1

[0033] A preparation method of a voriconazole intermediate racemate, the method comprising the following steps: adding methanol (7.0v / w, 140ml), 3-(6-chloro-5-fluoropyrimidin-4-yl) to a 500ml reaction flask -2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (51.12mmol, 20.00g), stirred and dissolved until clear, Add 5% Pd / C (1.02mmol, 2.18g) and aqueous sodium formate (153.36mmol, 10.43g) (purified water 2.0v / w, 40ml) into the reaction flask, add glacial acetic acid (30.67mmol, 1.53 g), replace with nitrogen three times, raise the temperature to 40-60°C and react for 6-7.5h, then cool down the reaction system to room temperature, filter, filter to dryness, concentrate the filtrate under reduced pressure, add purified water (5.0v / w, 100ml ), stirring to form a white suspension, adjusting the pH to 9-12 with aqueous sodium hydroxide solution, beating, suction filtration, and washing the filter cake with purified water until neutral. The filter cake was dried in a blast...

Embodiment 2

[0035] A kind of preparation method of voriconazole intermediate racemate, this method comprises the following steps: add methanol (7.0v / w, 2500ml), 3-(6-chloro-5-fluoropyrimidin-4-yl) in 5000ml reaction bottle -2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (91.20mmol, 350.00g), stirred and dissolved until clear, Add 5% Pd / C (1.82mmol, 38.81g) into sodium formate aqueous solution (364.8mmol, 248.10g) (purified water 2.0v / w, 700ml) into the reaction flask, add glacial acetic acid (45.60mmol, 27.38g ), pass through nitrogen protection, heat the oil bath to 60-75°C and react for 2 hours, cool the reaction system to room temperature, filter, and filter to dryness, the filtrate is concentrated under reduced pressure, and purified water (5.0v / w, 1750ml) is added Stir evenly, adjust the pH to 9-12 with aqueous sodium hydroxide solution, make a slurry, filter with suction, and wash the filter cake with purified water until neutral. The filter cake was dried in a blast ov...

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 preparation method of a voriconazole intermediate raceme, which comprises the following steps: step 1, adding 3-(6-chloro-5-fluoropyrimidine-4-yl)-2-(2, 4-difluorophenyl)-1-(1H-1, 2, 4-triazole-1-yl)-2-butanol into a solvent, stirring and dissolving until the solution is clear; and step 2, respectively adding palladium-carbon, formate and organic acid at room temperature, replacing with nitrogen for three times, heating to 40-80 DEG C, reacting for 1-7.5 hours, and cooling the reaction system to room temperature; and filtering, crystallizing and drying to obtain a finished product of the 2-(2, 4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1, 2, 4-triazole-1-yl)-2-butanol. According to the preparation method of the voriconazole intermediate raceme, sodium formate is used as a chemical hydrogen source in the preparation process, a purification process is improved, reaction conditions are mild and controllable, a large number of by-products do not appear in the reaction process, operation and post-treatment are simple, the product yield and quality are obviously improved, the production time and cost can be saved, and the method is suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to chemical industry field, especially a kind of preparation method of voriconazole intermediate racemate. Background technique [0002] Racemate 2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazol-1-yl)-2- Butanol is an important fine chemical raw material and pharmaceutical intermediate, with a CAS number of 182230-43-9 and a molecular formula of C 16 h 14 N 5 OF 3 , the molecular structure is: [0003] [0004] Existing racemate 2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazol-1-yl) There are many by-products in the preparation process of -2-butanol, especially large amino genotoxic impurities are produced, the product yield is low, and the production cost is increased. For this reason, the present invention proposes a racemate 2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazole Preparation of -1-yl)-2-butanol. Contents of the invention [0005] Aiming ...

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): C07D403/06
CPCC07D403/06
Inventor 郁慧於长权侯卫卫刘海峰王跃庄玉江邵津
Owner SHAANXI LICAI GROUP XIANYANG LICAI MEDICAL
Features
  • Generate Ideas
  • 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