Synthetic method of N-amino-3-azabicyclo[3,3,0]octane hydrochloride

A technology of octane hydrochloride and azabicycle is applied in the field of synthesis of pharmaceutical intermediates, and can solve the problems such as difficult disposal of waste, difficulty in stirring, and difficulty in disposal.

Inactive Publication Date: 2012-03-21
山东洪智生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, domestic patent 200810060128.1N-amino-3-azabicyclo[3,3,0]octane hydrochloride is prepared by reduction of N-amino-1,2-cyclopentane dicarboximide, and the yield is 78.7%; patent 200810061421.X is prepared by reacting a derivative of o-dimethylcyclopentane with hydrazine halide, and the yield does not exceed 85%; The consumption of the synthetic base of amino-3-azabicyclo[3,3,0]octane hydrochloride is too bi

Method used

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  • Synthetic method of N-amino-3-azabicyclo[3,3,0]octane hydrochloride

Examples

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Embodiment 1

[0010] Add 100g of nitroso compounds and 450g of industrial hydrochloric acid into a 2000ml reaction bottle, add 110g of zinc powder several times at 15°C under stirring, keep the reaction at 15°C for 7 hours, filter into a 5000ml reaction bottle, and add 10% hydrogen Sodium oxide solution is about 2000ml, adjust the pH value to 12-13, filter, wash the filter cake with water until neutral, drain, and dry to obtain 130g of zinc hydroxide, the filtrate is extracted with toluene 300ml×4, the extract is processed with about 100g of hydrochloric acid to adjust The pH value is 1~2, reflux under reduced pressure to separate the water until it is exhausted, cool to 5°C, filter, and dry the filter cake to obtain 112g of N-amino-3-azabicyclo[3,3,0]octane hydrochloride , yield 96.5%.

Embodiment 2

[0012] Add 120g of nitroso compounds and 550g of industrial hydrochloric acid into a 2000ml reaction bottle, add 115g of zinc powder several times at 10°C under stirring, keep the reaction at 20°C for 5 hours, filter into a 5000ml reaction bottle, add 15% hydrogen Potassium oxide solution is about 1700ml, adjust the pH value to 12-13, filter, wash the filter cake with water until neutral, drain, and dry to obtain 158g of zinc hydroxide, add xylene to the filtrate to extract 350ml×3, and extract about 120g of hydrochloric acid Adjust the pH value to 1-2, reflux under reduced pressure to divide the water until exhausted, cool to 7°C, filter, and dry the filter cake to obtain N-amino-3-azabicyclo[3,3,0]octane hydrochloride 133.2 g, yield 95.6%.

Embodiment 3

[0014] Add 100g of nitroso compounds and 440g of industrial hydrochloric acid into a 2000ml reaction bottle, add 95g of zinc powder in small amounts at 10°C for several times while stirring, keep the reaction at 18°C ​​for 6 hours, filter into a 5000ml reaction bottle, and add 15% hydrogen Sodium oxide solution is about 1900ml, adjust the pH value to 12-13, filter, wash the filter cake with water until neutral, drain, and dry to obtain 120g of zinc hydroxide, extract the filtrate with butanone 300ml×5, and process the extract with about 105g of hydrochloric acid Adjust the pH value to 1~2, reflux under reduced pressure to separate the water until exhausted, cool to 3°C, filter, and dry the filter cake to obtain N-amino-3-azabicyclo[3,3,0]octane hydrochloride 113g, yield 97.4%.

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Abstract

The invention discloses a synthetic method of an important intermediate of gliclazide, in particular to the synthetic method of N-amino-3-azabicyclo[3,3,0]octane hydrochloride. The N-amino-3-azabicyclo[3,3,0]octane hydrochloride is prepared by the following steps of: reducing N-nitroso-3-azabicyclo[3,3,0]octane through zinc powder and hydrochloric acid, alkalizing and dissociating through potassium hydroxide or sodium hydroxide, extracting through methylbenzene or dimethylbenzene and the like, acidulating through industrial hydrochloric acid to form salts, reducing pressure, reflowing and completely distributing water, cooling and crystallizing. The synthetic method has the advantages of simple process, small alkali consumption, low discharge of wastes, high yield and low cost; and the synthetic method can be used for co-generating zinc hydroxide used as an auxiliary agent of rubber and surgical ointment and is suitable for industrial production.

Description

technical field [0001] The invention relates to a synthesis method of N-amino-3-azabicyclo[3,3,0]octane hydrochloride, belonging to the technical field of pharmaceutical intermediate synthesis. Background technique [0002] Gliclazide is currently the most widely used hypoglycemic drug around the world, including my country. N-amino-3-azabicyclo[3,3,0]octane hydrochloride is an important intermediate in the synthesis of gliclazide. [0003] At present, domestic patent 200810060128.1N-amino-3-azabicyclo[3,3,0]octane hydrochloride is prepared by reduction of N-amino-1,2-cyclopentane dicarboximide, and the yield is 78.7%; patent 200810061421.X is prepared by reacting a derivative of o-dimethylcyclopentane with hydrazine halide, and the yield does not exceed 85%; The consumption of the synthetic base of amino-3-azabicyclo[3,3,0]octane hydrochloride is too big, forms complex compound, produces a large amount of waste, and is difficult to handle; And foreign literature J.Med.and...

Claims

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Application Information

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IPC IPC(8): C07D209/52C01G9/02C08K3/22A61K47/02
Inventor 赵海桥范兴山王飞龙穆子齐
Owner 山东洪智生物科技有限公司
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