Method for asymmetrically synthesizing norepinephrine bitartrate

A technology of norepinephrine and bitartrate, which is applied in the field of norepinephrine bitartrate, can solve the problems of low resolution rate of racemic norepinephrine, increased cost and production cycle, and high risk, achieving dangerous Effect of reduction, reduction of cost increase, low cost of raw materials

Active Publication Date: 2020-12-15
南京仁为医药科技有限公司
View PDF10 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] US20200048185 relates to a method for preparing racemic norepinephrine by palladium-carbon reduction, and then undergoes salt-forming and splitting to obtain norepinephrine bitartrate. The resolution rate of adrenaline is low, which increases the cost and production cycle, and causes a large pollution problem at the same time

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 asymmetrically synthesizing norepinephrine bitartrate
  • Method for asymmetrically synthesizing norepinephrine bitartrate
  • Method for asymmetrically synthesizing norepinephrine bitartrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037]Under the protection of nitrogen, dissolve 2.43g (64.31mmol) of sodium borohydride in 30ml of tetrahydrofuran, cool to 10°C, add 7g (64.31mmol) of trimethylchlorosilane dropwise, after the addition is complete, heat up to 65°C and react for 4h, cool To 10℃-15℃, add 1g of (R)-(+)-alpha,alpha-diphenylprolinol, dissolve 10g (53.59mmol) of chloroacetylcatechol in 30ml of tetrahydrofuran at the same temperature, and slowly drip Add the above reaction system, after the dripping is completed, the temperature is raised to 25℃-30℃ and react for 24h. After the reaction is completed by TLC, 1N hydrochloric acid is added dropwise to adjust the pH to 1-2, after the tetrahydrofuran is evaporated, ammonia water is added dropwise to adjust the pH to 8- 9. Suction filtration, the filter cake was washed twice with water, the filter cake was collected, and dried under vacuum at 40°C-50°C to obtain 9.8 g of Intermediate I, with a yield of 96.95% and an ee value of 98%.

Embodiment 2

[0039]Under the protection of nitrogen, dissolve 3.47g (64.31mmol) of potassium borohydride in 30ml of tetrahydrofuran, cool to 10°C, add 12.12g (80.39mmol) of triethylchlorosilane dropwise, after the dropwise addition is complete, heat up to 55°C for 7h, Cool to 15℃-20℃, add 1.5g R)-(+)-alpha,alpha-dibenzylprolinol, and dissolve 10g (53.59mmol) of chloroacetylcatechol in 30ml tetrahydrofuran at the same temperature, slowly Add dropwise to the above reaction system. After the dropwise addition is completed, the temperature is raised to 25°C-30°C for 24 hours. After the reaction is completed by TLC, 1N hydrochloric acid is added dropwise to adjust the pH to 1-2, tetrahydrofuran is evaporated to dryness, and ammonia water is added dropwise to adjust the pH to 8 -9, suction filtration, the filter cake was washed twice with water, the filter cake was collected, and dried under vacuum at 40°C-50°C to obtain 8g of intermediate I with a yield of 79.14% and an ee value of 95.3%.

Embodiment 3

[0041]Under the protection of nitrogen, dissolve 3.04g (80.39mmol) of sodium borohydride in 30ml of tetrahydrofuran, cool to 10°C, add 12.40g (64.31mmol) of triisopropylchlorosilane dropwise, after the addition is complete, heat up to 55°C for 7h , Cool to 15℃-20℃, add 2g of R)-(+)-alpha,alpha-dinaphthylprolinol, dissolve 10g (53.59mmol) of chloroacetylcatechol in 30ml of tetrahydrofuran at the same temperature, slowly Add dropwise to the above reaction system. After the dropwise addition is completed, the temperature is raised to 25°C-30°C for 24 hours. After the reaction is completed by TLC, 1N hydrochloric acid is added dropwise to adjust the pH to 1-2, tetrahydrofuran is evaporated to dryness, and ammonia water is added dropwise to adjust the pH to 8 -9, suction filtration, the filter cake was washed twice with water, the filter cake was collected, and dried under vacuum at 40°C-50°C to obtain 8.6 g of Intermediate I with a yield of 85.08% and an ee value of 93.5%.

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 preparation method for asymmetrically synthesizing norepinephrine bitartrate. The method is characterized by comprising the following steps: by using chloroacetyl catechol asa raw material, asymmetrically reducing carbonyl in the chloroacetyl catechol into hydroxyl, reacting with urotropine, hydrolyzing with hydrochloric acid to obtain R-norepinephrine, salifying rnorepinephrine and Ltartaric acid are salified to obtain norepinephrine bitartrate, wherein the total yield is larger than or equal to 86%, the ee value is larger than or equal to 95%, and the purity is larger than or equal to 99.6%. The method overcomes the defects in the prior art, and has the advantages that asymmetric reduction is adopted, so that the yield of norepinephrine bitartrate is increased,three wastes and the cost are reduced, and the method is suitable for industrial production.

Description

Technical field[0001]The present invention relates to a new method for asymmetric synthesis of norepinephrine bitartrate, in particular to the use of an asymmetric reduction catalyst to reduce chloroacetylcatechol to a key intermediate (I) required for the synthesis of norepinephrine bitartrate, After ammoniation and salt formation, high-purity norepinephrine bitartrate is synthesized.Background technique[0002]Norepinephrine, the scientific name 1-(3,4-dihydroxyphenyl)-2-aminoethanol, is a substance formed by removing the N-methyl group of epinephrine, and it belongs to catecholamines in chemical structure, formerly known as "norepinephrine" It is used to treat hypotension caused by acute myocardial infarction, cardiopulmonary bypass, pheochromocytoma resection, etc. It is often used as a blood pressure booster in first aid. It is a commonly used first aid drug in clinical practice.[0003]The current process for producing norepinephrine bitartrate has certain drawbacks. Most of them ...

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): C07C213/08C07C215/60C07C213/02C07C51/41C07C59/255C07C37/00C07C39/24
CPCC07C213/08C07C213/02C07D487/18C07C37/002C07C51/412C07B2200/07C07C215/60C07C39/24C07C59/255Y02P20/584
Inventor 陈杰任燕陈怡然
Owner 南京仁为医药科技有限公司
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