Amiodarone hydrochloride preparation method

A technology of amiodarone hydrochloride and compounds, which is applied in the field of medicine, can solve the problems of low yield and purity, and achieve the effects of high purity, simple process, and cheap and easy-to-obtain raw materials

Active Publication Date: 2017-11-24
烟台万润药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0022] Aiming at the problems of low yield and low purity caused by the above-mentioned preparation of amiodarone hydrochloride, the present invention provides a method for amiodar

Method used

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  • Amiodarone hydrochloride preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The synthesis of embodiment 1 amiodarone hydrochloride

[0050] Synthesis of compound shown in A, formula 3

[0051]

[0052] Add 276.7g (2.0mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 100g of N,N-dimethylformamide, and 300g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 320g of water was added, the water layer was separated, and the organic layer was washed with 320g of water Once, the solvent was evaporated at 0.09MPa / 80°C to obtain 190.2g of the compound represented by formula 3, with a GC purity of 98.8% and a yield of 95.0% (calculated as 2-hydroxybenzaldehyde).

[0053] Synthesis of compound shown in B, formula 4

[0054]

[0055] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 93.4g (0.88mol) of trim...

Embodiment 2

[0079] The synthesis of embodiment 2 amiodarone hydrochloride

[0080] Synthesis of compound shown in A, formula 3

[0081]

[0082] Add 332.0g (2.4mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 130g of N,N-dimethylformamide, 600g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 400g of water was added, the water layer was separated, and the organic layer was washed with 400g of water Once, the solvent was evaporated at 0.09MPa / 80 to obtain 197.2g of the compound shown in formula 3, with a GC purity of 98.6% and a yield of 98.5% (calculated as 2-hydroxybenzaldehyde).

[0083] B, the synthesis of formula 4 compounds

[0084]

[0085] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 127.2g (1.2mol) of trimethyl orthoforma...

Embodiment 3

[0109] The synthesis of embodiment 3 amiodarone hydrochloride

[0110] Synthesis of compound shown in A, formula 3

[0111]

[0112] Add 387.3g (2.8mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 140g of N,N-dimethylformamide, 600g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 500g of water was added, the water layer was separated, and the organic layer was washed with 500g of water Once, the solvent was evaporated at 0.09MPa / 80 to obtain 198.2g of the intermediate of formula 3 with a GC purity of 98.9% and a yield of 99.0% (calculated as 2-hydroxybenzaldehyde).

[0113] Synthesis of compound shown in B, formula 4

[0114]

[0115] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 169.8g (1.6mol) of trimethyl orthoform...

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Abstract

The invention belongs to the field of medicine, and especially relates to an amiodarone hydrochloride preparation method. The method takes 2-hydroxybenzaldehyde and 2-alkyl halohexoic acid ester as the raw materials to prepare 2-butylbenzofuran, 2-butylbenzofuran is taken as the raw material, and is subjected to the steps of friedel-crafts acylation, demethylation, iodination, etherification and salt forming to obtain the amiodarone hydrochloride. By employing the method, the raw materials have the advantages of low cost and easy acquisition, the process is simple, and 2-butylbenzofuran and amiodarone hydrochloride with high purity and high yield can be obtained, the cost is low, the waste water is little, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a preparation method of amiodarone hydrochloride. Background technique [0002] Amiodarone, also known as amiodarone, was first synthesized by Marly Nitrogen and Chemical Products Company in Belgium and applied for production in West Germany in 1961. It was originally introduced as a coronary artery dilator. In the 1970s, Singh discovered its electrophysiological mechanism of action. In 1976, Rosenbam took the lead in applying it to the treatment of antiarrhythmia. Amiodarone hydrochloride is the hydrochloride salt of amiodarone, and its structural formula is as follows: [0003] [0004] 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 negligible. Therefore, even long-term use of larger doses is safe. Amiodarone is absorbed from the intestinal tract and excreted ver...

Claims

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Application Information

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IPC IPC(8): C07D307/80
Inventor 杜体建乔仁国肖景超杨光李炬马振堂乔磊易朝辉
Owner 烟台万润药业有限公司
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