A kind of preparation method of terbutaline sulfate

A technology of terbutaline sulfate and acid binding agent is applied in the field of preparation of terbutaline sulfate, can solve the problems of expensive raw materials, long reaction steps, complicated operation, etc., and avoids high-risk and highly toxic reagents, reaction Mild conditions, long solution steps and low yield

Active Publication Date: 2022-07-12
ZHEJIANG PHARMA COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Purpose of the invention: In order to solve the technical problems in the existing synthesis process of terbutaline sulfate, such as expensive and difficult to obtain raw materials, use of high-risk and highly toxic reagents, long reaction steps, low yield, cumbersome operation and other technical problems, a terbutaline sulfate is provided Forest preparation method

Method used

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  • A kind of preparation method of terbutaline sulfate
  • A kind of preparation method of terbutaline sulfate
  • A kind of preparation method of terbutaline sulfate

Examples

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Effect test

Embodiment 1

[0033] A preparation method of terbutaline sulfate, specifically comprising:

[0034] (1) Preparation of 3,5-dibenzyloxyacetophenone

[0035] At room temperature, 100.0g (657.25mmol) of 3,5-dihydroxyacetophenone, 227.1g (1.64 mol) of anhydrous potassium carbonate, 1L of acetone and 174.7g (1.38 mol) of benzyl chloride were added successively in the reaction vessel. , and reacted at 50°C for 6h. The reaction solution was cooled to room temperature, filtered with suction, the filter cake was washed with acetone (2×100 mL), the combined filtrates were evaporated under reduced pressure to remove acetone, and the residue was recrystallized from methanol to obtain an off-white solid, namely 3,5-dibenzyloxybenzene 175.0 g of ethyl ketone, yield 80%.

[0036] 1 H NMR (300MHz, DMSO-d6): δ=7.32-7.47 (m, 10H), 7.18 (d, J=1.8Hz, 2H), 6.96 (t, J=1.8Hz, 1H), 5.16 (s, 4H) ),2.55(s,3H).

[0037] (2) Preparation of 3,5-dibenzyloxyacetophenone aldehyde

[0038]At room temperature, 100.0 g...

Embodiment 2

[0048] A preparation method of terbutaline sulfate, specifically comprising:

[0049] (1) Preparation of 3,5-dibenzyloxyacetophenone

[0050] At room temperature, 150.0g (985.88mmol) of 3,5-dihydroxyacetophenone, 313.4g (2.27 mol) of anhydrous potassium carbonate, 1L of acetone and 262.1g (2.07 mol) of benzyl chloride were successively added to the reaction vessel. , and reacted at 60°C for 4h. The reaction solution was cooled to room temperature, filtered with suction, the filter cake was washed with acetone (2×100 mL), the combined filtrates were evaporated under reduced pressure to remove acetone, and the residue was recrystallized from methanol to obtain an off-white solid, namely 3,5-dibenzyloxybenzene 268.7 g of ethyl ketone, yield 82%.

[0051] 1 H NMR (300MHz, DMSO-d6): δ=7.32-7.47 (m, 10H), 7.18 (d, J=1.8Hz, 2H), 6.96 (t, J=1.8Hz, 1H), 5.16 (s, 4H) ),2.55(s,3H).

[0052] (2) Preparation of 3,5-dibenzyloxyacetophenone aldehyde

[0053] At room temperature, 150.0 ...

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Abstract

The invention discloses a preparation method of terbutaline sulfate. The method adopts 3,5-dihydroxyacetophenone as a starting material, and is protected by a benzyl group to obtain 3,5-dibenzyloxyacetophenone , 3,5-dibenzyloxyacetophenone is brominated with copper bromide and oxidized with DMSO to obtain 3,5-dibenzyloxyacetophenone aldehyde, and then reductively aminated with tert-butylamine to generate 1-[3,5-dibenzyloxyacetophenone aldehyde (benzyloxy)phenyl]-2-(tert-butylamino)ethanol, and finally through hydrogenation debenzylation and sulfuric acid salification to obtain terbutaline sulfate. Compared with the prior art, the raw and auxiliary materials used in the present invention are all cheap and easy to obtain, avoid the use of high-risk and highly toxic reagents, have no high temperature and high pressure reaction, are easy to operate, have mild reaction conditions, and solve the problem of long steps and low yield in the prior art. , with security risks and other disadvantages.

Description

technical field [0001] The invention relates to a preparation method of terbutaline sulfate, and belongs to the technical field of terbutaline sulfate synthesis. Background technique [0002] Terbutaline Sulfate, also known as salbutamol, terbutaline, is an adrenergic agonist that selectively stimulates β2 receptors to relax bronchial smooth muscle and inhibit endogenous spasm-causing substances. The release of bronchial mucociliary epithelium increases the clearance of bronchial mucociliary epithelium in edema caused by endogenous mediators. It was first developed by AstraZeneca Pharmaceuticals Co., Ltd. and was produced and marketed abroad in 1988. Clinically, it is mainly used for the treatment of bronchospasm in bronchial asthma, asthmatic bronchitis and chronic obstructive pulmonary disease. [0003] At present, a number of synthetic processes for terbutaline sulfate have been reported at home and abroad, but there are certain technical problems, such as long process ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C215/60C07C213/00
CPCC07C45/61C07C213/02C07C213/00C07C49/84C07C49/86C07C217/70C07C215/60Y02P20/55
Inventor 姚晓敏贾姝姚晓坤吴静怡
Owner ZHEJIANG PHARMA COLLEGE
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