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Method for synthesizing sodium 2-carboxyphenylborate

A technology of sodium carboxyphenyl borate and methoxycarbonyl phenyl borate, which is applied in the field of synthesizing sodium 2-carboxyphenyl borate, can solve the problems of long steps, cumbersome operation, unsuitability for the preparation process of sodium 2-carboxyphenyl borate, etc., and achieve cost Low cost, easy to obtain raw materials, and easy operation

Inactive Publication Date: 2020-05-19
大连双硼医药化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The above-mentioned method steps are long, and operation is too loaded down with trivial details, is not suitable as the preparation technology of 2-carboxyphenyl borate sodium

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 2- Under the protection of nitrogen, put 280g THF, 43g methyl 2-bromobenzoate and trimethyl borate (1.5eq is the molar ratio) into a 500mL four-necked bottle, cool down to -85~-75℃, add Butyllithium n-hexane solution 60g1.1eq, after dripping, keep stirring for 2 hours, sample 10% hydrochloric acid to quench, and HPLC detects that the raw material is less than 6.5%. Stir naturally to raise the temperature to -20~15°C, add 99g of 10% hydrochloric acid aqueous solution dropwise to quench the reaction, the quenching process will release heat, the system temperature should be controlled below 0~5°C, pH=4~5, the system is stratified , separate the tetrahydrofuran layer and concentrate under reduced pressure, the water layer is extracted with 80 g of ethyl acetate each time, and the extraction is total 2 times, the ethyl acetate layer and the concentrated tetrahydrofuran layer are combined, washed once with 15-20 g of sodium chloride aqueous solution, and the organic phase is ...

Embodiment 2

[0021] The first step is the same as in Example 1

[0022] Add 29.5g of 2-methoxycarbonylphenylboronic acid and 60g of methanol into a 250mL reactor, and add 26.2g of 25% sodium hydroxide dropwise at a temperature of 45-50°C. After the dropwise addition, keep warm at 45-50°C for 2 hours, and check whether there are any raw materials left in the reaction solution in LC, and add sodium hydroxide if there is any. There is no remaining raw material for post-processing, vacuum distillation to no liquid, the obtained solid is added to the mother liquor acetone + new acetone for the first beating, a total of 60g, the temperature is raised to 50°C for beating, and then the temperature is gradually lowered to 0°C for beating for 0.5h, and the solid is obtained by filtration. Dry, a total of 32g, yield 95%, lc99.8%.

Embodiment 3

[0024] 3- Under nitrogen protection, put 280g THF, 43g methyl 2-bromobenzoate and 49g (1.28eq) triisopropyl borate into a 500mL four-necked bottle, cool down to -85~-75℃, add n-butyl Lithium-based n-hexane solution 60g1.1eq, after dripping, keep stirring for 2 hours, sample 10% hydrochloric acid to quench, and HPLC detects that the raw material is less than 1.6%. Naturally raise the temperature and stir to raise the temperature to -20~15°C, add dropwise 99g of 10% hydrochloric acid aqueous solution to quench the reaction, the quenching process will release heat, the system temperature should be controlled below 0~5°C, pH=4~5, the system will be layered, The tetrahydrofuran layer was separated and concentrated under reduced pressure, the water layer was extracted with 80 g of ethyl acetate each time, a total of 2 extractions, the ethyl acetate layer and the concentrated tetrahydrofuran layer were combined, washed once with 15-20 g of aqueous sodium chloride solution, and the org...

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PUM

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Abstract

The invention discloses a method for synthesizing sodium 2-carboxyphenylborate. The method comprises the following two steps of: 1) taking methyl 2-bromobenzoate as an initial raw material, through bromine removal by butyl lithium, carrying out a one-pot reaction with triisopropyl borate or trimethyl borate to obtain a product 2-methoxycarbonyl phenylboronic acid, and 2) hydrolyzing the 2-methoxycarbonyl phenylboronic acid in a sodium hydroxide methanol solution, and pulping with acetone to obtain sodium 2-carboxyphenylborate monohydrate. The method has the advantages of easily available raw materials, simple operation, safety, environmental protection, low cost and high yield.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing sodium 2-carboxyphenyl borate. Background technique [0002] Sodium 2-carboxyphenylborate has been widely used in drug synthesis as a coupling aid. There are not many synthesis of sodium 2-carboxyphenyl borate in the literature, there are DIPHARMA FRANCIS s.r.l. US2008 / 15357, 2008, A1Location in patent: Page / Page column 3-4 and Dipharma Francis S.r.l.EP1878735, 2008, A1, Location in patent: Page / Page column 6, both in the same method. [0003] The first step: use 2-bromobenzoic acid, react with thionyl chloride to form 2-bromobenzoyl chloride, then react with 1,1-dimethylamino alcohol to obtain amide, and then react the alcohol with thionyl chloride again The hydroxyl group becomes chlorine, and finally sodium hydroxide is added to close the ring to generate 2-bromo-4,4-dimethyloxazobenzene. [0004] The second step: react 2-bromo-4,4-dim...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
CPCC07F5/025
Inventor 刘启宾郑鹏
Owner 大连双硼医药化工有限公司