Synthetic method of memantine hydrochloride

A technique for synthesizing memantine hydrochloride, which is applied in the amidation reaction and method improvement field of synthesizing memantine hydrochloride, can solve problems such as thick reaction mixture and difficult stirring, and achieve simple post-reaction treatment, shortened process time, and improved efficiency effect

Inactive Publication Date: 2012-05-02
GUANGZHOU BOJI MEDICINE SERVICES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0025] Aiming at the deficiencies of the existing acetonitrile method for synthesizing memantine hydrochloride, the object of the present invention is to provide an optimized synthesis method of memantine hydrochloride for the treatment of dementia, which can effectively solve the problem of viscous reaction mixture in the amidation reaction. , stirring difficulties and a series of other problems caused by stirring difficulties

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  • Synthetic method of memantine hydrochloride
  • Synthetic method of memantine hydrochloride
  • Synthetic method of memantine hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0039] (1) Preparation of 1-bromo-3,5-dimethyladamantane

[0040] Take 200g of 1,3-dimethyladamantane in a three-necked bottle, connect the drying pipe and exhaust gas absorption device. Heated to 75°C, and 190ml of bromine was added dropwise. React for 26 hours and cool to room temperature. Add 400 ml of dichloromethane, and add saturated sodium bisulfite solution under ice cooling until the mixture turns light yellow. Static separation, the organic phase was obtained. The aqueous phase was extracted with dichloromethane (80ml×3), the organic phases were combined, washed with saturated sodium carbonate solution until neutral, and then washed with 100ml of saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, and distilled under reduced pressure to collect 80 °C fraction, 275 g of colorless transparent liquid was obtained, with a yield of 92.9%.

[0041] (2) Preparation of 1-acetamido-3,5-dimethyladamantane

[0042] Take 31.5ml of acetonit...

Embodiment 2

[0046] (1) Preparation of 1-bromo-3,5-dimethyladamantane

[0047] With embodiment 1 (1).

[0048] (2) Preparation of 1-acetamido-3,5-dimethyladamantane

[0049] Take 32ml of acetonitrile and 5ml of glacial acetic acid, put them into a three-necked bottle, and add 30ml of concentrated sulfuric acid dropwise under cooling in an ice bath. Control the temperature of the mixture below 20°C. After the dropwise addition, 10 g of 1-bromo-3,5-dimethyladamantane (dissolved in 10 ml of glacial acetic acid) was added dropwise while controlling the internal temperature below 55°C. After the dropwise addition, it was heated to 55°C, the reaction solution changed from colorless to light yellow, and gradually turned into vermilion. After about 30 minutes, the color faded and the reaction solution turned into light yellow. The reaction was continued at 55°C for 24 hours with stirring. Cool to room temperature, pour into 200ml of water, and white crystals precipitate out. After suction fil...

Embodiment 3

[0053] (1) Preparation of 1-bromo-3,5-dimethyladamantane

[0054] With embodiment 1 (1).

[0055] (2) Preparation of 1-acetamido-3,5-dimethyladamantane

[0056] Take 300ml of acetonitrile and 380ml of glacial acetic acid, put them into a three-necked bottle, and add 260ml of concentrated sulfuric acid dropwise under ice cooling. Control the temperature of the mixture below 20°C. After the dropwise addition, 100.4 g of 1-bromo-3,5-dimethyladamantane (dissolved in 100 ml of glacial acetic acid) was added dropwise while controlling the internal temperature below 55°C. After the dropwise addition, it was heated to 55°C, the reaction solution changed from colorless to light yellow, and gradually turned into vermilion. After about 30 minutes, the color faded and the reaction solution turned into light yellow. The reaction was continued at 55° C. for 24 hours with stirring. Cool to room temperature, pour into 2000ml of water, and white crystals precipitate out. After suction fil...

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Abstract

The invention discloses a synthetic method of memantine hydrochloride serving as a medicament for treating dementia. The method comprises the following steps of: reacting halogenated dimethyladamantane with nitrile, concentrated sulfuric acid and organic acid to obtain 1-acetamido-3,5-dimethyladamantane crystal serving as an intermediate for synthesizing memantine hydrochloride; hydrolyzing 1-acetamido-3,5-dimethyladamantane with alcohol and alkali to generate raw memantine; and extracting and salting to obtain memantine hydrochloride. In the method, the organic acid is taken as a solvent, so that the problems of low yield, difficulty in stirring and a series of problems caused by difficulty in stirring are solved; compared with an original process, the method has the advantages that: five steps for distilling the solvent under reduced pressure, adding water, extracting methylene dichloride, recovering the solvent under reduced pressure and recrystallizing are reduced, the reaction post-treatment operation is simplified greatly, and reaction post-treatment is easy and convenient; operation is easier and more convenient, so that the time consumption of a memantine hydrochloride synthesizing process is lowered, and the efficiency is increased; compared with an original process, the method has the advantages that: the step for extracting methylene dichloride serving as an organic solvent is eliminated, so that higher economic efficiency and environmental friendliness are achieved; and more importantly, the acetamide reaction yield is increased from lower than 70 percent to over 90 percent.

Description

Technical field [0001] The present invention involves a synthesis method for the treatment of drug hydrochloric acid hydrochloric acid in the treatment of dementia. Specifically, it is a method of improving the enonation reactions for synthetic iconic acid hydrochloride. Background technique [0002] There are many synthesis methods for the U.S. Vajrayana Hydrochloride.The synthesis method with 1,3-di methal as a raw material has been retrieved, mainly the following four types. [0003] Method 1: acetylene method.1-bromo-3,5-di methane Vales occur with concentrated sulfuric acid and react with acetamide with acetyl. [0004] [0005] Method 2: Nitrotic catalytic hydrogenation method.1,3-di methane vathemidized, catalytic hydrogenation, and salt methalum hydrochloride. [0006] [0007] Method 3: 法 脲 method.1-bromo-3,5-di methar alkane reactions and chimotol reactions generate 3,5-di methar alkane after hydrolysis and salt to get oxyline hydrochloride. [0008] [0009] Meth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C211/38C07C209/62
Inventor 董翀翎周瑞明马仁强
Owner GUANGZHOU BOJI MEDICINE SERVICES
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