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

A kind of preparation method of 2-deoxy-2,2-difluoro-d-erythro-pentofuranose-3,5-dibenzoate

A technology of dibenzoate and pentofuranose, which is applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of unstable overall yield, high and low phase difference, no α-isomer purity, and harsh conditions, so as to facilitate the transformation , Reduce production costs, reduce the effect of risk

Active Publication Date: 2020-06-26
江苏八巨药业有限公司
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, the Chinese patent (authorized announcement number: CN101899072B) discloses a method for preparing gemcitabine intermediates based on sodium borohydride reduction, including 2-deoxy-2,2-difluoro-3,5-dibenzoyl-D- Reduction of ribofuranolide to 2-deoxy-2,2-difluoro-3,5-dibenzoyl-D-ribofuranose in the presence of glacial acetic acid and Lewis acid using sodium borohydride as reducing agent , and the Lewis acid is cerium trichloride, but it has higher requirements for the catalytic reduction system, so that under the mixed system of glacial acetic acid and Lewis acid in combination with sodium borohydride, the borane that may be formed can work, through The control of glacial acetic acid is used to suppress the products of side reactions and avoid the problem of ring opening. The conditions are harsh and not conducive to control; Low and unstable, while the reaction does not have issues specific to the α-isomer purity of the product

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 preparation method of 2-deoxy-2,2-difluoro-d-erythro-pentofuranose-3,5-dibenzoate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] At room temperature, 150 mL of THF solvent was added to the reactor, and then 2-deoxy-2,2-difluoro-D-erythro-1-furanulose-3,5-dibenzoyl ester 20 g ( 0.054mol), sodium borohydride 2.2g (0.06mol) and PPO-CBS immobilized catalyst 2.0g, then, under agitation, slowly add methanol 6g dropwise, and control the temperature at 20°C to 30°C during the dropwise addition; After the addition is complete, continue to control the temperature at about 22°C for heat preservation reaction for 3 hours. After the reaction, add hydrochloric acid dropwise to the reaction solution to adjust the pH value of the system to 6.5, stir for 10 minutes, filter, and recover the solid PPO-CBS immobilized catalyst. Apply mechanically, the filtrate is left to stand for 30min, and then the organic phase is collected in layers; the aqueous layer can be extracted twice with 50mL of tetrahydrofuran, and the combined organic phase is washed once with 50mL of saturated aqueous sodium bicarbonate solution, left ...

Embodiment 2

[0024]At room temperature, 112 mL of THF solvent was added to the reactor, and then 20 g of 2-deoxy-2,2-difluoro-D-erythro-1-furanulose-3,5-dibenzoyl ester was added ( 0.054mol), sodium borohydride 2.2g (0.06mol) and PPO-CBS immobilized catalyst 1.8g, then, under stirring conditions, slowly add methanol 6g dropwise, and control the temperature at 20°C to 25°C during the dropwise addition; After the addition is complete, continue to control the temperature at about 22°C for heat preservation reaction for 3.5 hours. After the reaction, add hydrochloric acid dropwise to the reaction solution to adjust the pH value of the system to 6.5, stir for 10 minutes, filter, and recover the solid PPO-CBS immobilized catalyst. Apply mechanically, the filtrate is left to stand for 30min, and then the organic phase is collected in layers; the aqueous layer can be extracted twice with 50mL of tetrahydrofuran, and the combined organic phase is washed once with 50mL of saturated aqueous sodium bic...

Embodiment 3

[0026] At room temperature, 250 mL of THF solvent was added to the reactor, and then 20 g of 2-deoxy-2,2-difluoro-D-erythro-1-furanulose-3,5-dibenzoyl ester was added ( 0.054mol), sodium borohydride 2.4g (0.065mol) and PPO-CBS immobilized catalyst 2.2g, then, under the condition of stirring, slowly add methanol 8g dropwise, and control the temperature at 25°C to 30°C during the dropwise addition; After the addition is complete, continue to control the temperature at about 27°C for heat preservation reaction for 2.5 hours. After the reaction, add hydrochloric acid dropwise to the reaction solution to adjust the pH value of the system to 6.5, stir for 10 minutes, filter, and recover the solid PPO-CBS immobilized catalyst. Apply mechanically, the filtrate is left to stand for 30min, and then the organic phase is collected in layers; the aqueous layer can be extracted twice with 50mL of tetrahydrofuran, and the combined organic phase is washed once with 50mL of saturated aqueous so...

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 2-deoxy-2, 2-difluoro-D-red-3, 5-dibenzoate and belongs to the technical field of medicine intermediate synthesis. In order to solve the problems of poor selectivity and safety in the prior art, the invention provides the preparation method of the 2-deoxy-2, 2-difluoro-D-red-3, 5-dibenzoate, which comprises carrying out redox reaction on 2-deoxy-2,2-difluoro-D-red-1-ketofuranose-3, 5- dibenzoate under the combined action of immobilized catalysts of sodium borohydride and PPO-CBS to convert to the product of 2-deoxy-2, 2-difluoro-D-red-3, 5-dibenzoate. The method has the advantage of high chiral selectivity, improves the integral conversion rate, plays a better asymmetric reduction role, and achieves the purpose that the purity of the isomer is more than 95%.

Description

technical field [0001] The invention relates to a preparation method of 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate, belonging to the technical field of pharmaceutical intermediate synthesis. Background technique [0002] Gemcitabine hydrochloride is a difluoronucleoside antimetabolite anticancer drug that disrupts cell replication, and has a good inhibitory effect on human leukocytes and human tumor xenografts. And the important intermediate of synthesizing gemcitabine at present is 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate, which plays a key role in the process of synthesizing gemcitabine. Therefore, the research on the synthesis of the 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate is also high at present. [0003] In the prior art, 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-3, the preparation method of 5-dibenzoate is mostly based on 2-deoxy-2,2-difluoro- D-erythro-1-furanulose-3,5-dibenzoyl ester is used as raw material...

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): C07H15/18C07H1/00
CPCC07B2200/07C07H1/00C07H15/18
Inventor 张锦涛程加铭王福军刘玉坤卢文才汪东海
Owner 江苏八巨药业有限公司
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