Chiral phosphamide synthesizing method

A synthesis method and phosphoramide technology, which is applied in the field of synthesizing chiral phosphoramides with a single configuration of the phosphorus chiral center, can solve the problems of difficult operation and waste, and achieve the effects of easy acquisition, mild reaction conditions, and low raw material prices

Inactive Publication Date: 2009-06-03
XIAMEN UNIV
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method is not easy to operate. Not every product can be disassembled, and half o...

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
  • Chiral phosphamide synthesizing method
  • Chiral phosphamide synthesizing method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] In a 25mL round-bottomed flask, put 0.5mmol (Rp) menthoxyphenyl hydrogen phosphite and 30mg ammonia water in 10mL acetonitrile, keep the temperature at 0°C, and finally add 0.5mmol of C 2 Cl 6 Dissolve the solution in 5ml of acetonitrile and continue to stir overnight. After the reaction is over, remove the solvent under reduced pressure to obtain a crude product. Purification by column chromatography was carried out under the condition of eluent whose polarity was petroleum ether: ethyl acetate = 5:1-1:2 to obtain the product with a yield of 75%.

Embodiment 2

[0023] In a 25mL round-bottomed flask, dissolve 0.5mmol (Rp) menthyl isopropoxyhydrogen phosphite and 1mmol phenylalanine in 5mL of water, add 5mL of acetonitrile, keep the temperature within 8°C, and then add Add 1 equivalent of triethylamine, and finally add 20 mmol of CCl dropwise 4 , continue to stir overnight, after the reaction is over, remove acetonitrile and other low-boiling organic matter under reduced pressure, remove unreacted menthyl isopropoxyhydrogen phosphite with 10 mL of dichloromethane, and use 1mol.L -1 dilute hydrochloric acid to adjust the pH value to about 3, dichloromethane 10mL extraction to obtain the crude product, the polarity of petroleum ether: ethyl acetate = 5:1 ~ 1:2 eluent conditions for column chromatography separation and purification, The product was obtained with a yield of 70%.

Embodiment 3

[0025] In a 25mL round bottom flask, 0.5mmol (Rp) menthoxybutoxyhydrogen phosphite and 1mmol diethylamine were dissolved in 10mL dichloromethane, the temperature was kept at -40°C, and then 1 equivalent of tris Ethylamine, finally dropwise the dichloromethane solution of the diisopropylamino chloride of 1mmol, react 3 hours after completion of dropwise addition, after reaction finishes, remove low-boiling point organic matter under reduced pressure, at polarity is sherwood oil: ethyl acetate= Purification by column chromatography was carried out under the condition of 5:1-1:2 eluent to obtain the product with a yield of 70%.

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 discloses a chiral phosphamide synthesizing method, relating to a chiral phosphamide, in particular to a method for synthesizing chiral phosphamide in which phosphorus has single chiral center configuration. The invention provides the chiral phosphamide synthesizing method which has the advantages of low-price and easily obtained raw materials, high productivity, no easy racemization, simple operation and is suitable for large-scale production. Under the existence of halogenating agents and organic base, the chiral phosphamide, in which phosphorus has single chiral center configuration, or phosphinate and unhindered amina, primary amine or secondary amine reacts in a solvent to generate corresponding chiral phosphamide in which phosphorus has single chiral center configuration.

Description

technical field [0001] The present invention relates to a chiral phosphoramide, in particular to a method for synthesizing a chiral phosphoramide with a single configuration of the phosphorus chiral center, which comprises making the phosphorus chiral Chiral hydrogen phosphite (phosphonite) ester with a single configuration of the sex center reacts with amine compounds in a solvent. More specifically, the method uses hexachloroethane, etc. as a halogenating agent, and triethylamine as a catalyst and an acid-binding agent, so that chiral hydrogen phosphite (phosphine) ester and free ammonia, primary amine or secondary amine Reaction in a solvent generates a chiral phosphoramide with a single configuration of the phosphorus chiral center. Background technique [0002] Phosphoramides have a variety of important uses in medicine, such as being used as prodrugs to help drugs enter the cell membrane, and then taking off the phosphoryl group to release the original drug; directly ...

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): C07F9/24C07F9/36C07F9/44
Inventor 赵玉芬王刚唐果许鹏翔韩立彪
Owner XIAMEN UNIV
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