A kind of preparation method of terbutaline sulfate

A technology of terbutaline sulfate and acetic anhydride, which is applied in the preparation of amino compounds from amines, bulk chemical production, organic chemistry, etc., can solve the problems of high cost, achieve low cost, high yield, and avoid the effect of hydrogenation high pressure

Active Publication Date: 2017-03-22
SHANDONG DYNE MARINE BIOTECHCAL PHARM HLDG CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The present invention aims to solve the technical problems of high-risk operations such as high-pressure hydrogenation and high-risk reagents such as methyllithium and azomethane in the existing preparation method of terbutaline sulfate, and provides a route with mild reaction, high safety, A method for preparing terbutaline sulfate that avoids high-risk operations such as hydrogenation and high pressure, has simple process, high yield, low cost, high product purity, cheap and easy-to-obtain raw and auxiliary materials, and is suitable for industrial production

Method used

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  • A kind of preparation method of terbutaline sulfate

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Effect test

Embodiment 1

[0023] The preparation method of terbutaline sulfate, concrete steps comprise:

[0024] (1) Dissolve 3,5-dihydroxyacetophenone (1.52Kg, 10mol) in 10L of dichloromethane under nitrogen protection, add acetic anhydride (2.04Kg, 20mol), cool down to 20°C, and add trichloride in batches Aluminum (2.67kg, 20mol), the temperature is controlled between 20-25°C, the addition is completed in 2h, and the reaction is carried out at 20°C for 0.5h. After the reaction was completed, 10L of water was slowly added, stirred for 15min, allowed to stand for stratification, and the organic phase of the lower layer was washed with 10L of water once, and dichloromethane was evaporated under reduced pressure at 40°C to obtain a light brown crystalline powder, which was obtained after drying under reduced pressure at 45°C. 3,5-diacetoxyacetophenone 1.96Kg.

[0025] (2) Dissolve 3,5-diacetoxyacetophenone (1.02Kg, 5mol) in 5L of chloroform, add (800g, 5mol) bromine dropwise at 25°C, add in about 2 hou...

Embodiment 2

[0029] The preparation method of terbutaline sulfate, concrete steps comprise:

[0030] (1) Dissolve 3,5-dihydroxyacetophenone (1.52Kg, 10mol) in 10L of dichloromethane under nitrogen protection, add acetic anhydride (2.24Kg, 22mol), cool down to 20°C, and add trichloride in batches Aluminum (2.93kg, 22mol), the temperature is controlled between 20-25°C, the addition is completed in 2h, and the reaction is carried out at 20°C for 0.5h. After the reaction was completed, 10L of water was slowly added, stirred for 15min, allowed to stand for stratification, and the organic phase of the lower layer was washed with 10L of water once, and dichloromethane was evaporated under reduced pressure at 40°C to obtain a light brown crystalline powder, which was obtained after drying under reduced pressure at 45°C. 3,5-diacetoxyacetophenone 2.01Kg.

[0031](2) Dissolve 3,5-diacetoxyacetophenone (1.02Kg, 5mol) in 5L of chloroform, add (840g, 5.25mol) bromine dropwise at 25°C, add about 2.5h, ...

Embodiment 3

[0035] The preparation method of terbutaline sulfate, concrete steps comprise:

[0036] (1) Dissolve 3,5-dihydroxyacetophenone (1.52Kg, 10mol) in 10L of dichloromethane under nitrogen protection, add acetic anhydride (2.14Kg, 21mol), cool down to 15°C, and add trichloride in batches Aluminum (2.80kg, 21mol), the temperature is controlled between 15-20°C, the addition is completed in 2h, and the reaction is carried out at 20°C for 0.5h. After the reaction is completed, slowly add 10L of water, stir for 15min, let stand to separate layers, wash the lower organic phase with 10L of water once, evaporate dichloromethane to dryness under reduced pressure at 40°C to obtain a light brown crystalline powder, and dry under reduced pressure at 45°C to obtain 3,5-diacetoxyacetophenone 1.73Kg.

[0037] (2) Dissolve 3,5-diacetoxyacetophenone (1.02Kg, 5mol) in 5L of chloroform, add (821g, 5.13mol) bromine dropwise at 20°C, add about 2.5h, and add Then add 2.5L of 10% sodium carbonate solut...

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Abstract

The invention relates to a preparation method of terbutaline sulphate. The technical problems that according to an existing preparation method of terbutaline sulphate, high-pressure hydrogenation and other high-risk operations, and lithium methide, azomethane and other high-risk reagents exist, and cost is high are solved through the preparation method. 3,5-resacetophenone serves as a raw material, and terbutaline sulphate is obtained through hydroxyl protection, the bromination reaction, carbonyl reduction, the condensation reaction and sulphating. The preparation method can be suitable for industrially-produced terbutaline sulphate.

Description

technical field [0001] The invention belongs to the field of chemical drug synthesis, and in particular relates to a preparation method of terbutaline sulfate. Background technique [0002] Terbutaline sulfate, also known as hydroxyalbutaline and terbutaline, is mainly used for the treatment of bronchospasm in bronchial asthma, asthmatic bronchitis and chronic obstructive pulmonary disease. The product is white or off-white crystalline powder; odorless, or slightly smells of acetic acid; gradually changes color when exposed to light. The product is soluble in water, slightly soluble in methanol, almost insoluble in chloroform. [0003] The synthesis of terbutaline sulfate reported in the literature mainly contains the following routes: [0004] Route 1: Chinese Journal of Pharmaceutical Industry, 1990, 30(1):4-6. In this route, 3,5-dihydroxybenzoic acid is esterified, the hydroxyl group is protected with benzyl, and then hydrolyzed to obtain 3,5-dibenzyloxybenzoic acid. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C215/34C07C209/68
CPCY02P20/55
Inventor 蔡琨岳德仁
Owner SHANDONG DYNE MARINE BIOTECHCAL PHARM HLDG CO LTD
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