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Method for preparing amiodarone hydrochloride

An amiodarone hydrochloride and acid-catalyzed technology, which is applied in the field of medicine, can solve the problems of difficult crystallization, high treatment costs, and low purification yield, and achieve the effects of reducing three wastes, fewer by-products, and simple operation

Active Publication Date: 2021-10-22
SUZHOU HOMESUN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But, also there are many problems in this route: 1) the use of aluminum chloride in Friedel-Crafts reaction, can produce a lot of three wastes, and treatment cost is higher; Precipitation of crystallization, low purification yield

Method used

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  • Method for preparing amiodarone hydrochloride
  • Method for preparing amiodarone hydrochloride
  • Method for preparing amiodarone hydrochloride

Examples

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preparation example Construction

[0033] The preparation method of the present invention can be expressed as follows:

[0034]

Embodiment 1

[0036] Dissolve 2-butylbenzofuran 1 (17.4g, 100mmol) in 1,2-dichloroethane (120mL), add anhydrous ferric chloride (1.62g, 10mmol), then add p-acetoxy Benzaldehyde (18.1g, 110mmol) was reacted at 80°C for 5 hours. After the reaction, 50 mL of water was added, stirred for 30 minutes, the organic layer was separated, washed with 20 mL of saturated sodium bicarbonate solution, and the solution was evaporated to dryness to obtain a crude compound of formula 8, which was directly used in the next reaction. 1 H NMR (400MHz, CDCl 3 )δ7.80(s,2H),7.42(d,J=8.0Hz,1H),7.34–7.31(m,1H),7.25–7.20(m,1H),7.14(td,J=7.6,1.0Hz ,1H),5.96(s,1H),2.79(t,J=7.6Hz,2H),2.39(s,3H),1.77–1.69(m,2H),1.45-1.36(m,2H),0.96( t,J=7.2Hz,3H).

[0037] The above crude compound of formula 8 was dissolved in methanol (200 mL), added elemental iodine (81.3 g, 0.32 mol) and sodium hydroxide (24.0 g, 0.60 mol), and reacted at 65° C. for 2 hours. After the reaction, add saturated sodium sulfite (10mL) and dilute hydroc...

Embodiment 2

[0040] Dissolve 2-butylbenzofuran 1 (17.4g, 100mmol) in dichloromethane (120mL), add anhydrous zinc chloride (10mmol), then add p-acetoxybenzaldehyde (18.1g, 110mmol), React at 90°C for 3 hours. After the reaction, 50 mL of water was added, stirred for 30 minutes, the organic layer was separated, washed with 20 mL of saturated sodium bicarbonate solution, and the solution was evaporated to dryness to obtain a crude compound of formula 8, which was directly used in the next reaction.

[0041] The above crude compound of formula 8 was dissolved in isopropanol (200 mL), added elemental iodine (81.3 g, 0.32 mol) and potassium hydroxide (0.60 mol), and reacted at 50° C. for 5 hours. After the reaction, add saturated sodium sulfite (10mL) and dilute hydrochloric acid (2M, 10mL) to wash, extract with dichloromethane, combine the organic layers and evaporate to dryness, then recrystallize with dichloromethane to obtain the compound of formula 4, the two-step yield is 67% .

[0042]T...

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Abstract

The invention discloses a method for preparing amiodarone hydrochloride, which comprises the following steps: by taking 2-butylbenzofuran and p-acetoxybenzaldehyde as raw materials, carrying out aldol reaction under Lewis acid catalysis and heating conditions, simultaneously carrying out hydroxyl oxidation, deacetylation and iodination reaction on the product in the presence of iodine and alkali, and then reacting the product with N, N-diethyl chloroethylamine, and salifying to obtain amiodarone hydrochloride. According to the method, only a catalytic amount of Lewis acid is needed, strong acidic aluminum chloride is not needed, reaction conditions are milder, byproducts are few, post-treatment is easy, and three wastes are greatly reduced; the whole route is simple to operate, the used reagents are cheap, easy to obtain and non-toxic, and the method is very suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of amiodarone hydrochloride. Background technique [0002] Amiodarone hydrochloride (Amiodarone) is a class III antiarrhythmic drug widely used in the treatment and prevention of ventricular and supraventricular arrhythmias. Its α- and β-adrenoceptor blockade and mild I and IV antiarrhythmic drug properties, the curative effect on severe and fatal arrhythmia is very significant. In addition, amiodarone can also affect thyroxine metabolism. The toxicity of amiodarone is very small, the lethal dose of intravenous injection is 10 times of the therapeutic dose, and the lethal dose of oral administration is very large, so the toxicity can be ignored. Therefore, even long-term large doses of amiodarone are safe. This product is characterized by a long half-life, after being absorbed from the intestinal tract, the excretion is very slow, and 16-34% re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/80
CPCC07D307/80
Inventor 陆红彬樊超杨颖栋陆志丹
Owner SUZHOU HOMESUN PHARMA
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