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Method for preparing 2-(2-ethoxyphenoxy) ethyl bromide

A technology of ethoxyphenoxy and ethoxyphenol, which is applied in the field of purification of the intermediate by acid-base back extraction and recrystallization, the preparation and purification of the intermediate 2-ethyl bromide, to improve the purity , avoid the vacuum distillation process, and optimize the preparation process

Inactive Publication Date: 2014-03-26
NAT INST OF PHARMA R & D CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0024] The object of the present invention is to aim at the problems existing in the synthetic method of tamsulosin hydrochloride, and propose a kind of tamsulosin hydrochloride key intermediate 2-(2) with simple reaction steps, easy and convenient aftertreatment and purification, and more suitable for industrialized production. The preparation method of -ethoxyphenoxy) ethyl bromide

Method used

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  • Method for preparing 2-(2-ethoxyphenoxy) ethyl bromide
  • Method for preparing 2-(2-ethoxyphenoxy) ethyl bromide
  • Method for preparing 2-(2-ethoxyphenoxy) ethyl bromide

Examples

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Embodiment 1

[0045] Under nitrogen protection, dissolve 100g of catechol in 230ml of water. After dissolving at room temperature, slowly add 20% aqueous sodium hydroxide solution dropwise to adjust the pH value to 8-9, then add 14.5g of tetrabutylammonium bromide, and heat up To 70 DEG C, begin to drop slowly 145ml diethyl sulfate (completely dropwise in about 4 hours), add 20% sodium hydroxide solution at any time during the dropping process, keep the pH of the reaction solution at 9-10, and keep The temperature of the reaction solution was 75-80° C., and the dropwise addition was completed (thin-layer chromatography showed that the raw material disappeared).

[0046] The reaction solution was lowered to room temperature, and concentrated hydrochloric acid was added dropwise to adjust the pH value of the reaction solution to 2-3, extracted twice with toluene (400ml×2), the organic phases were combined, and washed with 400ml saturated sodium chloride and 400ml distilled water respectively. ...

Embodiment 2

[0048]Under nitrogen protection, dissolve 100g of catechol in 230ml of water. After dissolving at room temperature, slowly add 20% aqueous sodium hydroxide solution dropwise to adjust the pH value to 8-9, then add 14.5g of tetrabutylammonium bromide, and heat up To 70 DEG C, begin to drop slowly 145ml diethyl sulfate (completely dropwise in about 4 hours), add 20% sodium hydroxide solution at any time during the dropping process, keep the pH of the reaction solution at 9-10, and keep The temperature of the reaction solution was 75-80° C., and the dropwise addition was completed (thin-layer chromatography showed that the raw material disappeared).

[0049] The reaction solution was lowered to room temperature, concentrated hydrochloric acid was added dropwise to adjust the pH value of the reaction solution to 2-3, extracted twice with cyclohexane (400ml×2), the organic phases were combined, and 400ml of saturated sodium chloride and 400ml of distilled water were respectively use...

Embodiment 3

[0051] Dissolve 88g of o-ethoxyphenol in 176ml of 1,2-dibromoethane, add 10.27g of tetrabutylammonium bromide, raise the temperature to 75°C, then slowly add 640ml of 10% sodium hydroxide solution dropwise (about 6 hours dropwise), keep the pH value of the reaction solution between 9-10, dropwise is complete (thin-layer chromatography shows that the raw material disappears).

[0052] Separate the organic layer, wash the organic layer with 200ml of saturated sodium chloride solution and 200ml of water respectively, concentrate the organic layer to dryness, and recrystallize the crude product with 200mL of ethanol to obtain 2-(2-ethoxyphenoxy)ethyl Bromine 110g, the yield is 70.5%.

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Abstract

The invention provides a new method for synthesizing and purifying 2-(2-ethoxyphenoxy) ethyl bromide. The method comprises the following steps: by taking catechol as a starting raw material, obtaining high-purity o-ethoxyphenol by using an acid-alkali back extraction method instead of an existing reduced-pressure distillation post-treatment way, then enabling o-ethoxyphenol to react with 1, 2-dibromoethane to obtain a crude product of 2-(2-ethoxyphenoxy) ethyl bromide, and obtaining high-purity 2-(2-ethoxyphenoxy) ethyl bromide which can be used as an intermediate for preparing tamsulosin hydrochloride by using an ethanol recrystallization post-treatment method instead of the existing reduced-pressure distillation post-treatment way. According to the method, the existing reduced-pressure distillation post-treatment process is avoided, the purity of the intermediate is improved, and the method is more suitable for industrial production. The purity and the yield of 2-(2-ethoxyphenoxy) ethyl bromide obtained by using the method are improved, the method is more suitable for industrial production, the purity achieves above 98% and the total yield is above 70%.

Description

technical field [0001] The invention relates to the fields of medicine and chemical industry, and relates to a preparation and purification process of an intermediate 2-(2-ethoxyphenoxy)ethyl bromide, in particular to the purification of the intermediate by acid-base back extraction and recrystallization. body method. Background technique [0002] As an intermediate, 2-(2-ethoxyphenoxy)ethyl bromide can be used for the preparation of tamsulosin hydrochloride, a drug for treating benign prostatic hyperplasia. Tamsulosin hydrochloride was successfully developed by Japan's Yamanouchi Pharmaceutical Co., Ltd., and was approved by the FDA in July 1992 under the trade name Harnal. Since then, it has jointly sold tamsulosin hydrochloride with Boehringer Ingelheim and Abbott, and was approved by the FDA in 1997 under the trade name Flomax. The drug has definite curative effect and high safety, and is the first-line drug for treating benign prostatic hyperplasia. [0003] 2-(2-Eth...

Claims

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Application Information

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IPC IPC(8): C07C43/225C07C41/16
CPCC07C41/16
Inventor 张淑兰王毅飞辛丕明宗利斌
Owner NAT INST OF PHARMA R & D CO LTD
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