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

Preparation technology of (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione

A technology of oxazolidinedione and benzyloxycarbonyl, which is applied in the field of chemical synthesis and production, and can solve the problems of large influence on yield, easy ring opening and the like

Active Publication Date: 2019-09-06
荆门医药工业技术研究院 +1
View PDF10 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] After several tests on the experimental conditions, it was found that the problem must be solved by heating in a neutral to slightly alkaline environment, but (S)-4- Isopropyloxazole-2,5-dione (Formula 6) is easy to open the ring in an alkaline environment, and the combination of solvent and weak base has a great influence on the yield

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 technology of (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione
  • Preparation technology of (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione
  • Preparation technology of (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The synthesis of embodiment 1 N-benzyloxycarbonyl-L-valine

[0050] Get 1.17Kg (10mol) of L-valine, 5L of sodium hydroxide solution of 2mol / L, 1.06Kg (10mol) sodium carbonate and add in the 20L reactor, start stirring, after the L-valine dissolves completely, dissolve the solution When the temperature dropped below 0°C, 5L of 1,4-dioxane solution containing 2.05Kg (12mol) of benzyl chloroformate was added dropwise, and the temperature of the solution was kept below 20°C during the dropping process. After the reaction, the reaction solution was extracted with 2.5L of dichloromethane, the organic phase was discarded, the water phase was cooled to below 10°C, concentrated hydrochloric acid was added dropwise until the pH = 2, and then stirred at 10°C for 30min, a large amount of white solid was precipitated, and filtered with suction , the filter residue was washed with water, and the white solid was dried in a vacuum oven to obtain 2.35Kg of white N-benzyloxycarbonyl-L-va...

Embodiment 2

[0052] The synthesis of embodiment 2 (S)-3-benzyloxycarbonyl-4-isopropyl-2,5-oxazolidinedione

[0053] Get 1.17Kg (10mol) of L-valine, 5L of sodium hydroxide solution of 2mol / L, 1.06Kg (10mol) sodium carbonate and add in the 20L reactor, start stirring, after the L-valine dissolves completely, dissolve the solution When the temperature dropped below 0°C, 5L of 1,4-dioxane solution containing 2.05Kg (12mol) of benzyl chloroformate was added dropwise, and the temperature of the solution was kept below 20°C during the dropping process. After the reaction is complete, the reaction solution is extracted with 2.5 L of dichloromethane, the organic phase is discarded, the water phase is cooled to below 10°C, concentrated hydrochloric acid is added dropwise until pH=2, the mixture is extracted 3 times with 3 L of dichloromethane, and the organic phases are combined. The organic phase was washed with 3L saturated brine, dried over anhydrous sodium sulfate for 12 hours, filtered, and the...

Embodiment 3

[0054] The synthesis of embodiment 3 (S)-3-benzyloxycarbonyl-4-isopropyl-2,5-oxazolidinedione

[0055] Get 1.17Kg (10mol) of L-valine, 5L of sodium hydroxide solution of 2mol / L, 1.06Kg (10mol) sodium carbonate and add in the 20L reactor, start stirring, after the L-valine dissolves completely, dissolve the solution When the temperature dropped below 0°C, 5L of 1,4-dioxane solution containing 2.05Kg (12mol) of benzyl chloroformate was added dropwise, and the temperature of the solution was kept below 20°C during the dropping process. After the reaction is complete, the reaction solution is extracted with 2.5 L of dichloromethane, the organic phase is discarded, the water phase is cooled to below 10°C, concentrated hydrochloric acid is added dropwise until pH=2, the mixture is extracted 3 times with 3 L of dichloromethane, and the organic phases are combined. The organic phase was washed with 3L saturated brine, dried over anhydrous sodium sulfate for 12 hours, filtered, and the...

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 provides a preparation technology of (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione. The (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione can serve as a valganciclovir hydrochloride intermediate. The technology includes the following operations that an L-valine starting material reacts with benzyl chloroformate to generate N-carbobenzoxy-L-valine; the N-carbobenzoxy-L-valinereacts with N,N-carbonyl diimidazole (CDI) to generate the (S)-3-carbobenzoxy-4-isopropyl-2,5-oxazolidinedione. The preparation technology is simple in method, purification is easy, the process is stable, the quality is controllable, the product yield is greatly improved, environmental pollution is not caused, and the technology is suitable for industrial mass production.

Description

technical field [0001] The invention relates to a preparation process of (S)-3-benzyloxycarbonyl-4-isopropyl-2,5-oxazolidinedione, which belongs to the field of chemical synthesis and production. Background technique [0002] Valganciclovir hydrochloride (valganciclovir hydrochloride) (formula 4) is a kind of oral anti-cytomegalovirus infection medicine researched and developed by Roche Company of Switzerland, the paper " the development of valganciclovir hydrochloride that Zhao Shikui et al. Synthesis", introduced a hydroxyl group of the ganciclovir derivative N, O-di(trityl) ganciclovir (formula 5) and (S)-3-benzyloxycarbonyl- 4-isopropyl-2,5-oxazolidinedione (Formula 3) is condensed, and the trityl protecting group is removed by trifluoroacetic acid in 2,2,2-trifluoroethanol, and then acidified, Hydrogen reduction to obtain valganciclovir hydrochloride. [0003] [0004] Currently, the preparation of (S)-3-benzyloxycarbonyl-4-isopropyl-2,5-oxazolidinedione (Formula 3...

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): C07D263/44
CPCC07D263/44C07B2200/07Y02P20/55
Inventor 罗磊李立威王乐
Owner 荆门医药工业技术研究院
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