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Preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepine-2-keto

A technology of benzazepine and benzonitrogen, applied in the field of preparation of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one, which can solve the complicated purification , many by-products, low yield and other problems, to achieve the effect of simple production process, low production cost and high purity of finished products

Active Publication Date: 2015-11-04
ZHEJIANG BOJU NEW MATERIALS CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The above several methods mainly have the following disadvantages: 1, there are many by-products, and the product is inconvenient to separate
[0005] 2. The yield is low and the purification is more complicated
[0006] 3. This route has a low yield and is not suitable for industrial production
[0007] 4. There are many reaction steps and the operation is complicated

Method used

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  • Preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepine-2-keto

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Effect test

Embodiment 3

[0035] The preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in this embodiment includes the preparation stage of α-tetralone, 2-bromo-3 , 4-dihydro-N-hydroxy-(2H)-naphthylimine preparation stage and 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepine-2-one stage, Specific steps are as follows:

[0036] 1) α-tetralone preparation stage

[0037] Add γ-butyrolactone, benzene, and anhydrous aluminum trichloride in a molar ratio of 1:10:3 into the dry reaction kettle, slowly heat up to 65°C under stirring, and keep the temperature for 28 hours; 25 parts by weight of 6% hydrochloric acid solution are hydrolyzed, layered, and washed to neutrality; then excess benzene is removed by distillation, and high-vacuum rectification is used to obtain α-tetralone;

[0038] 2) 2-bromo-3,4-dihydro-N-hydroxy-(2H)-naphthalene imine preparation stage

[0039] Add α-tetralone and methanol in a molar ratio of 1:25 into the dry reactor, and under stirring, add bromine with a molar rat...

Embodiment 2

[0043] The preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in this embodiment includes the preparation stage of α-tetralone, 2-bromo-3 , 4-dihydro-N-hydroxy-(2H)-naphthylimine preparation stage and 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepine-2-one stage, Specific steps are as follows:

[0044] 1) α-tetralone preparation stage

[0045] Add γ-butyrolactone, benzene, and anhydrous aluminum trichloride in a molar ratio of 2:17:6 into the dry reaction kettle, slowly heat up to 75°C under stirring, and keep the temperature for 20 hours; 25 parts by weight of 6% hydrochloric acid solution are hydrolyzed, layered, and washed to neutrality; then excess benzene is removed by distillation, and high-vacuum rectification is used to obtain α-tetralone;

[0046] 2) 2-bromo-3,4-dihydro-N-hydroxy-(2H)-naphthalene imine preparation stage

[0047] Add α-tetralone and methanol in a molar ratio of 1:50 into a dry reactor, and under stirring, add bromine dropwise at a temp...

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Abstract

The invention discloses a preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-benzazepine-2-keto. The preparation method comprises the following stages: alpha-tetralone preparation stage, 2-bromo-3,4-dihydro-N-hydroxy-(2H)-naphthalimide preparation stage and 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepine-2-keto, wherein the alpha-tetralone preparation stage comprises the following steps: after mixing gamma-butyrolactone, benzene and aluminum chloride anhydrous, raising the temperature to be 60-90 DEG C, and preserving the temperature for reaction for 5-30 hours; after the reaction is finished, performing hydrolysis, layering and washing on 25 parts of 6% hydrochloric acid solution until neutral; and then distilling to remove excessive benzene, and performing high vacuum rectification to obtain alpha-tetralone. Then, the finished product is finally prepared through a bromination reaction, an oximation reaction and a beckmann rearrangement reaction, the purity of the finished product is high, and the yield is as high as more than 90%. Moreover, the production technology is simple, the production cost is low, and the pollution is little.

Description

technical field [0001] The invention relates to a preparation method of 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one. Background technique [0002] 3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one is an intermediate in the synthesis of benazepril hydrochloride. Benazepril hydrochloride is the first-line antihypertensive drug recommended by the World Health Organization. It is a chiral drug with good clinical efficacy, high safety and small side effects among the current international antihypertensive drugs of angiotensin converting enzyme inhibitors. . [0003] The synthetic method of literature report mainly contains: 1, use chromium acetate and 2-methyl-5-ethylpyridine composite catalyst, take air as oxidant, carry out normal pressure continuous liquid phase oxidation, reaction temperature 130 ℃, tetralin and oxygen The molar ratio of the compound is 1:0.6, the residence time is 60-70min, the selectivity of generating 1-tetralone is about 90%, and the main by-product...

Claims

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Application Information

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IPC IPC(8): C07D223/16
CPCC07D223/16
Inventor 龚华银周俊周邦福
Owner ZHEJIANG BOJU NEW MATERIALS CO LTD
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