A kind of method for synthesizing vilanterol intermediate in mixed solvent

A technology of mixed solvents and intermediates, which is applied in the field of drug synthesis, can solve the problems of poor selectivity and achieve the effects of improving selectivity, simplifying the difficulty of post-processing, and simple post-processing

Active Publication Date: 2021-09-14
ANHUI DEXINJIA BIOPHARM
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Analyzing the reason therein, it is not difficult to find that adding sodium borohydride in the acetic acid solvent first generates sodium triacetoxy borohydride, although the sodium triacetoxy borohydride that generates is less active than sodium borohydride, it is still active in protic solvents. Has high reactivity, resulting in poor selectivity of the reaction

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 method for synthesizing vilanterol intermediate in mixed solvent
  • A kind of method for synthesizing vilanterol intermediate in mixed solvent
  • A kind of method for synthesizing vilanterol intermediate in mixed solvent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 5-bromoacetyl-2-hydroxybenzaldehyde (200g) into a 5L three-necked flask, add 1,2-dichloroethane (1.5L), propionic acid (500mL), start stirring, and cool down to 5-10°C , within half an hour, add sodium borohydride (21.8g) in small amounts in batches. After the addition is complete, the liquid phase is controlled in the middle, and the remaining raw materials are less than 1%. Add 1L of water to the reaction system, stir at 0-5°C for 1 hour, and filter , washed with 500mL of water and dried to obtain 185g of white solid with a yield of 92% and a purity of 98%, of which over-reduction products accounted for 1.2%.

Embodiment 2

[0024] Add 5-bromoacetyl-2-hydroxybenzaldehyde (200g) into a 5L three-necked flask, add propionic acid (500mL), tetrahydrofuran (1.5L), start stirring, cool down to 5-10°C, within half an hour, a small amount of . Add sodium borohydride (21.8g) in batches. After the addition is complete, the liquid phase is controlled in the middle, and the remaining raw materials are less than 1%. Add 1L of water to the reaction system, stir at 0-5°C for 1 hour, filter, wash with 500mL of water, and dry. 190 g of white solid was obtained with a yield of 94% and a purity of 97.3%, of which over-reduced products accounted for 1.9%.

Embodiment 3

[0026] Add 5-bromoacetyl-2-hydroxybenzaldehyde (200g) into a 5L three-necked flask, add methanol (650mL), 1,2-dichloroethane (1.35L), start stirring, cool down to 5-10°C, Within half an hour, add sodium borohydride (21.8g) in small amounts in batches. After the addition is complete, the liquid phase is controlled in the middle, and the remaining raw materials are less than 1%. Add 1L of water to the reaction system, stir at 0-5°C for 1 hour, and filter. Washed with 500mL of water and dried to obtain 181g of white solid with a yield of 90% and a purity of 98%. Among them, over-reduction products accounted for 1.3%.

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 method for synthesizing an intermediate of vilanterol in a mixed solvent, belonging to the field of drug synthesis. The method obtains 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethan-1-ketone by reducing 5-bromoacetyl-2-hydroxybenzaldehyde with sodium borohydride. The invention reduces in a mixed solvent, improves the selectivity and yield of the reaction, has simple aftertreatment, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis and relates to a method for synthesizing vilanterol intermediate 2-bromo-1-[4-hydroxyl-3-(hydroxymethyl)phenyl]ethan-1-one in a mixed solvent. Background technique [0002] Bronchial asthma is a typical chronic respiratory disease with a high incidence and a wide distribution worldwide. It is estimated that by 2025, the number of patients worldwide will increase to 400 million. At present, the average incidence rate of asthma in my country is 2.1%, about 30 million people, and it is increasing year by year. In the European Union, the annual cost of asthma treatment is about 40 billion euros. In the United States, the annual direct economic cost of asthma is approximately $29.5 billion. The pathogenesis of asthma is complicated, and the traditional treatment methods have long treatment cycle, slow effect and high mortality rate, which not only cause the loss of labor force, decrease the quality of l...

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): C07C45/64C07C49/84
CPCC07C45/64C07C49/84
Inventor 郑庚修汪崇文高令峰张启龙卢伟阳
Owner ANHUI DEXINJIA BIOPHARM
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