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Method for preparing formyl phenylboronic acid

A technology of aldehyde phenylboronic acid and halogenated phenylboronic acid, which is applied in the field of synthesis of fine chemical intermediates, and can solve the problems of many impurities and difficult purification

Active Publication Date: 2015-11-11
CANGZHOU PURUI DONGFANG SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the synthesis of this method, the aldehyde group needs to be protected in advance, and the reaction also needs to be carried out at ultra-low temperature. When the synthesis is scaled up according to this method, the product has many impurities and is difficult to purify.

Method used

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  • Method for preparing formyl phenylboronic acid
  • Method for preparing formyl phenylboronic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Synthesis of p-bromophenylboronic acid trimer (formula II, X=p-Br):

[0019] In a 1L three-necked flask equipped with a reflux water separation device, add p-bromophenylboronic acid (201 g, 1.0 mol) and 700 ml of n-heptane, heat to reflux water separation, and when the system separates about 17.5-18.5 grams of water, And when the system no longer has water to continue to separate, stop the reaction. After cooling down, the heptane was distilled to stagnant liquid to obtain the crude p-bromophenylboronic acid trimer, which contained about 2-5% heptane at this time. directly into the next reaction.

[0020] Synthesis of p-aldehydophenylboronic acid:

[0021] Under nitrogen protection, the p-bromophenylboronic acid trimer obtained above was added to 600 ml of anhydrous tetrahydrofuran to dissolve evenly, and then transferred to a 2 L three-necked flask, and then dimethylformamide (80.4 g, 1.1 mol) was added. Then lower the temperature of the system to below -70°C, and s...

Embodiment 2

[0023] Synthesis of m-bromophenylboronic acid trimer (formula II, X=m-Br):

[0024] In a 1L three-necked flask equipped with a reflux water separation device, add m-bromophenylboronic acid (201 g, 1.0 mol) and 600 ml of toluene, heat to reflux water separation, when the system separates about 17.5-18.5 grams of water, and the system The reaction was stopped when no more water continued to separate. After cooling down, the heptane was distilled to stasis to obtain the crude m-bromophenylboronic acid trimer, which contained about 5-10% toluene at this time. directly into the next reaction.

[0025] Synthesis of m-aldophenylboronic acid:

[0026] Under nitrogen protection, the m-bromophenylboronic acid trimer obtained above was added to 600 ml of anhydrous tetrahydrofuran to dissolve evenly, then transferred to a 2 L three-necked flask, and dimethylformamide (80.4 g, 1.1 mol) was added. Then lower the temperature of the system to below -70°C, and slowly add 440 ml (1.1 moles) ...

Embodiment 3

[0028] Synthesis of o-bromophenylboronic acid trimer (formula II, X=o-Br):

[0029] In a 1L three-necked flask equipped with a reflux water separation device, add o-bromophenylboronic acid (201 grams, 1.0 mol) and 600 milliliters of toluene, heat to reflux water separation, when the system separates about 17.5-18.0 grams of water, and the system The reaction was stopped when no more water continued to separate. After cooling down, the heptane was distilled to stasis to obtain the crude m-bromophenylboronic acid trimer, which contained about 5-10% toluene at this time. directly into the next reaction.

[0030] Synthesis of o-aldehyde phenylboronic acid:

[0031] Under nitrogen protection, the o-bromophenylboronic acid trimer obtained above was added to 600 ml of anhydrous tetrahydrofuran to dissolve evenly, then transferred to a 2 L three-necked flask, and then dimethylformamide (87.7 g, 1.2 mol) was added. Then cool the system down to -70°C to -80°C, and start to slowly add...

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Abstract

The invention discloses a method for preparing formyl phenylboronic acid, which comprises the following steps: heating halogenated phenylboronic acid in toluene or heptane under reflux for dewatering to form a tripolymer, mixing the tripolymer with dimethylformamide, dropwisely adding n-butyllithium at low temperature to react by a one-pot process, hydrolyzing with hydrochloric acid, and recrystallizing to obtain the formyl phenylboronic acid. The method is simple to operate, avoids the process of separating the intermediate after formyl protection in the conventional technique, has high universality, can obtain favorable yield for ortho-, meta- and para- formyl phenylboronic acids, and is beneficial to scale-up production.

Description

technical field [0001] The invention relates to a method for preparing aldehyde phenylboronic acid, which belongs to the field of synthesis of fine chemical intermediates. Background technique [0002] In recent years, the use of Suzuki coupling reactions for the synthesis of key drug intermediates has become more and more common. For example, p-aldehyde phenylboronic acid is used in the synthesis of the powerful protease inhibitor atazanavir, a new drug on the market. [0003] atazanavir [0004] At present, the method of synthesizing aldehydophenylboronic acid starts from bromobenzaldehyde, first protects the acetal with trimethyl orthoformate or ethylene glycol, then exchanges with butyl lithium for bromine lithium, and then reacts with trimethyl borate to acidify Hydrolysis yields the target product. In the synthesis of this method, the aldehyde group needs to be protected in advance, and the reaction also needs to be carried out at ultra-low temperature. When the amp...

Claims

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Application Information

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IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 冷延国桂迁张进
Owner CANGZHOU PURUI DONGFANG SCI & TECH
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