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Method for synthesizing N-butyl-glucosamine

A synthesis method and glucosamine technology, applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of many by-products, low conversion rate, and low product yield, and achieve mild reaction conditions, easy reaction, and good product quality Effect

Inactive Publication Date: 2005-05-04
ZHEJIANG MEDICINE CO LTD XINCHANG PHAMACEUTICAL FACTORY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A large number of experiments have proved that due to the harsh reaction conditions in this patented method, the yield of the product obtained is low and the quality is poor.
In addition, from the analysis of the reaction mechanism, using Pd-C as a catalyst, hydrogenation is easy to polymerize glucose, resulting in low conversion rate and many by-products. It is difficult to use Pd-C as a catalyst to prepare N-butyl-glucosamine. chemical production

Method used

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  • Method for synthesizing N-butyl-glucosamine
  • Method for synthesizing N-butyl-glucosamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Embodiment 1: the preparation of active nickel catalyst

[0017] Add 250 g of 20-40 mesh aluminum-nickel alloy (containing 50% nickel) and 2 L of deionized water into a 5 L beaker. Cool the temperature in the beaker to below 5°C with ice-salt water. Slowly add 400 g of analytically pure sodium hydroxide, and control the feeding rate so that the reaction temperature does not exceed 5°C. After the addition, the reaction was continued at -5 to 5°C for 30 minutes. Alkaline water was replaced with deionized water until the pH was 7; and then replaced with absolute ethanol 6 times to obtain 120 g of the required active nickel.

Embodiment 2

[0018] Example 2: Synthesis of N-butyl-glucosamine

[0019] A) Feeding: In a 1L autoclave, add 100 g (0.5 mol) of D-glucose monohydrate, 38 g (0.53 mol) of n-butylamine, and then add 800 ml of a solvent of 90% methanol (containing 10% water). After nitrogen replacement, 5 g of the active nickel catalyst prepared in Example 1 was added, and high-purity hydrogen was blown in to keep the hydrogen pressure at 2-3 MPa. Slowly heat up to 35°C for reaction.

[0020] B) Reaction: Control the reaction temperature to 35-45° C., the hydrogen pressure to 2-4 MPa, and react for 10 hours. TLC is used to track the reaction. The glucose point disappears, and the reaction is terminated.

[0021] C) post-treatment: after the reaction is finished, release the hydrogen pressure and replace with nitrogen. The material is discharged and filtered, and the filter residue is spent active nickel catalyst, which is stored in deionized water and recovered for mechanical use after treatment. The light ...

Embodiment 3

[0022] Example 3: Synthesis of N-butyl-glucosamine

[0023] A) Feeding: In a 2L autoclave, add 199g (1mol) of D-glucose monohydrate, 80g (1.09mol) of n-butylamine, and then add 1500ml of 85% isopropanol solvent (containing 15% water). After nitrogen replacement, 15 g of the active nickel catalyst prepared in Example 1 was added, and high-purity hydrogen was blown in to keep the hydrogen pressure at 2-3 MPa. Slowly heat up to 35°C for reaction.

[0024] B) Reaction: Control the reaction temperature to 35-45° C., the hydrogen pressure to 2-4 MPa, and react for 12 hours. The reaction was followed by TLC, and the glucose spot disappeared, and the reaction was terminated.

[0025] C) post-treatment: after the reaction is finished, release the hydrogen pressure and replace with nitrogen. The material is discharged and filtered, and the filter residue is spent active nickel catalyst, which is stored in deionized water and recovered for mechanical use after treatment. The light re...

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Abstract

The invention relates to a kind of synthesizing method of midbody N- butyl- glucosamine, a medicine to therapy Gaucher I disease. The existing method has harsh requirement of reaction condition, low product yield, many by-product, and bad quality, so it is difficult to realize industrialization production. The reaction steps of the invention are as follows: A) Stuff casting: in autoclave, add D-glucose and ortho-butylamine according to molar ratio of D-glucose / ortho-butylamine with 1 / 1.05-1.10; then add 70-95% alcohols solvent with 5-10 times weight of glucose; and after nitrogen displace, add activity nickel catalyst with 5-10% weight of glucose; inject high purity hydrogen, keep hydrogen pressure to 2-3Mpa, and then intensify the temperature slowly; B) Reaction: control reaction temperature in 35-45deg.C, hydrogen pressure in 2-4Mpa, and reaction by 10-15 hours; C) Get white pulverous solid by after-treatment. The synthesizing method of the invention can make the reaction easy to take, and it generates by-product and other impurity badly, and also it has high conversion rate, more than or equal to 98% purity, high quality of product generated, so it adapts to industrialization production.

Description

【Technical field】 [0001] The invention relates to a synthesis method of a drug intermediate, in particular to a synthesis method of N-butyl-glucosamine, an important intermediate of Miglustat, a medicine for treating Gaucher type I disease. 【Background technique】 [0002] N-butyl-glucamine is an important intermediate in the synthesis of Miglustat, a drug for the treatment of Gaucher type I disease. Its English name is N-butyl-glucamine, and its structural formula is as follows: [0003] [0004] N-Butyl-glucosamine. [0005] At present, N-butyl-glucosamine has no ready-made products sold domestically or internationally, and its industrial production is very important for the synthesis of Miglustat, a drug for the treatment of Gaucher type I disease. EP0477160 discloses a synthetic method of N-butyl-glucosamine. This patent uses 4% Pd-C as a catalyst, and uses glucose and butylamine as raw materials to obtain N-(butyl) by hydrogenation in an autoclave. - Glucosamine. P...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C213/08C07C215/10
Inventor 陈鹏叶伟东胡微胡三明
Owner ZHEJIANG MEDICINE CO LTD XINCHANG PHAMACEUTICAL FACTORY
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