Phenylethanolamine-based beta receptor agonist synthesis method

A technology of phenylethanolamine and a synthesis method, which is applied in chemical instruments and methods, preparation of organic compounds, preparation of aminohydroxy compounds, etc., can solve the problems of complicated operation, high cost, low atom utilization rate, etc., and achieves cheap and easy-to-obtain raw materials, The effect of high atom utilization, simple and efficient synthesis method

Active Publication Date: 2019-06-21
上海安谱璀世标准技术服务有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there are few published documents on the synthesis method of β-receptor agonists, and the operation is complicated, the cost is high, and the utilization rate of atoms is low, and it is difficult to use the general route to obtain a variety of phenylethanolamine compounds. In view of the shortcomings of the existing synthesis route, It is necessary to provide a general method for synthesizing a variety of phenylethanolamine compounds with simple routes, cheap raw materials, and high atom utilization. The synthesized products can be used as standard reagents for the determination of β-receptor agonists to meet the requirements of my country's food safety. testing needs

Method used

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  • Phenylethanolamine-based beta receptor agonist synthesis method
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  • Phenylethanolamine-based beta receptor agonist synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] The synthetic method of 4-amino-3,5-dichloroacetophenone (Clenbuterol)

[0040]

[0041] Weigh 7.9g (59.2mmol) NCS in a 250ml three-neck flask, add 60ml MeCN, stir to dissolve, and slowly drop 4-aminoacetophenone (4g, 29.6mmol) dissolved in 50ml acetonitrile into the reaction with a constant pressure dropping funnel device, the dropwise addition was completed in half an hour, and stirred at room temperature for 3 hours. Rotary evaporate most of the solvent, add ethyl acetate and stir to dissolve, wash with 50ml pure water 3 times each time, collect the organic phase, and dry over anhydrous sodium sulfate. After filtration, the solvent was spin-dried to obtain 4.8 g of the main product acetophenone intermediate 4-amino-3,5-dichloroacetophenone, and the yield was 80%; at the same time, 0.9 g of by-product 4-amino-3-chloroacetophenone was obtained. g, the productive rate is 18%, which can be used in Example 5 as the raw material for the preparation of bromoclobuterol. ...

Embodiment 2

[0052] Synthetic method of 4-amino-3,5-dibromoacetophenone (bromobuterol)

[0053]

[0054] Weigh 11.6g, 65.1mmol N-bromosuccinimide (NBS) in a 250ml three-necked flask, add 60mlMeCN, stir to dissolve, and use a constant pressure dropping funnel to dissolve 4g, 29.6mmol 4-amino Acetophenone was slowly dropped into the reaction device, and the dropwise addition was completed in half an hour, and stirred at room temperature for 3 hours. Rotary evaporate most of the solvent, add ethyl acetate and stir to dissolve, wash 3 times with 50ml pure water, collect the organic phase, and dry over anhydrous sodium sulfate. After filtration, the solvent was spin-dried to obtain 6.9g of acetophenone intermediate main product 4-amino-3,5-dibromoacetophenone, and the yield was 80%; at the same time, 1.2g of by-product 4-amino-3-bromoacetophenone was obtained Ketones, with a yield of 20%, can be used in Examples 3 and 4 as raw materials for the preparation of sibuterol and cimaterol.

[00...

Embodiment 3

[0066] The synthetic method of 4-amino-3-bromoacetophenone (sibuterol)

[0067]

[0068] Weigh 4g (29.6mmol) of 4-aminoacetophenone into a 250ml three-neck flask, add 40ml of MeCN, stir to dissolve, and slowly drop 5.8g (32.6mmol) of NBS dissolved in 50ml of acetonitrile into the reaction device with a constant pressure dropping funnel , The dropwise addition was completed in half an hour, and stirred at room temperature for 3 hours. Rotary evaporate most of the solvent, add ethyl acetate and stir to dissolve, wash 3 times with 50ml pure water each time, collect the organic phase, and dry over anhydrous sodium sulfate. After filtration, the solvent was spin-dried to obtain 4.5 g of the main product of acetophenone intermediate, 4-amino-3 bromoacetophenone, with a yield of 71%; at the same time, 1.2 g of by-product 4-amino-3,5-dibromoacetophenone was obtained , the yield is 14%, and can be used in Example 2 as a raw material for the synthesis of brobuterol.

[0069] Synthe...

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Abstract

The invention discloses a phenylethanolamine-based beta receptor agonist synthesis method, which comprises: S1: dissolving 4-aminoacetophenone in an organic solvent, carrying out a halogenation reaction with an electrophilic substitution reagent at a benzene ring to generate a halobenzene intermediate, and carrying out a nucleophilic substitution reaction on the halobenzene intermediate and a cyaniding agent in an organic solvent or water under the catalysis of a metal catalyst to generate an acetophenone intermediate; S2, carrying out a carbonyl alpha bromination reaction on the acetophenoneintermediate and cupric bromide in an organic solvent to generate an alpha-bromoacetophenone intermediate; S3, carrying out a reaction on the alpha-bromoacetophenone intermediate and tert-butylamine or isopropylamine in an organic solvent to generate an acetophenone amine intermediate; and S4, carrying out a reaction on the acetophenone amine intermediate and a reducing hydrogenation reagent in anorganic solvent to generate a phenylethanolamine-based beta receptor agonist. According to the present invention, the synthesis method has characteristics of simpleness, high efficiency, inexpensiveand easily-available raw materials and high atom utilization rate, the chemical purity of the synthesized product is more than 99%, and the food safety testing requirements are met.

Description

technical field [0001] The invention relates to the technical field of chemical engineering, in particular to a synthesis method of a phenylethanolamine beta receptor agonist. Background technique [0002] With the continuous improvement of human living standards, people pay more and more attention to food safety. However, food safety issues are not optimistic, especially animal-derived food safety issues, which have become a global issue, and veterinary drug residues are the cause of animal The main cause of food safety problems from origin. Veterinary drug residues are a type of chemical risk, which cannot be recognized by consumers with their senses. Therefore, it is of great significance to strengthen the detection of veterinary drug residues to protect human health. [0003] Beta-receptor agonists can be used clinically to treat asthma-like conditions in humans and animals, and are similar to adrenaline-like phenylethanolamines in chemical structure. In addition, addi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C213/00C07C215/68C07C253/30C07C255/59
Inventor 王易刘慧艳陈武炼
Owner 上海安谱璀世标准技术服务有限公司
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