Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid

A kind of technology of chlorobenzoic acid and monobromine, applied in the field of preparation of 5-bromo-2-chlorobenzoic acid, can solve problems such as unsuitable for industrialized production, affecting production application, increasing production cost, etc. little effect

Active Publication Date: 2019-07-12
河北合佳医药科技集团股份有限公司
View PDF7 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is described in CN107954852A that sodium periodate solution is used as the brominated reagent to complete the process, but a large amount of iodine-containing waste water is produced in the later stage, which is difficult to handle. At the same time, the use of sodium periodate increases the production cost and is not suitable for industrial production; patent CN104744227A reports Carry out monobromination reaction in NBS (N-bromosuccinimide) / sulfuric acid system to obtain the method for 5-bromo-2-chlorobenzoic acid, the method reaction process is simple, raw material is easy to get, and improves 2- The selectivity of the bromination process of chlorobenzoic acid, but the selectivity of 5-bromo-2-chlorobenzoic acid is generally only 60~70%, and there is still about 10% of the generation of 4-bromo-2-chlorobenzoic acid impurities , the impurity is similar in polarity to the product, and it is difficult to remove it by conventional methods. The product with ideal purity can only be obtained after multiple recrystallizations, resulting in a low yield of the product, which affects production and application

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid
  • Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid
  • Preparation method of high-selectivity 5-bromo-2-chlorobenzoic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Add 4.7g (0.03mol) of 2-chlorobenzoic acid (0.03mol), concentrated sulfuric acid (40mL), and 0.936g (0.012mol) of sodium sulfide to a 250mL four-necked flask in sequence, stir at 30°C for 20 minutes until the solution is clear, then add 5.334g N-bromosuccinimide (0.03mol), continue to react at 30°C for 10 minutes, then slowly pour the solution into 80mL ice-water bath for crystallization to obtain crude 5-bromo-2-chlorobenzoic acid. The filter cake was put into a 250mL four-neck flask, 24mL of methanol and 36mL of water were added, the temperature was raised to 60°C, cooled naturally, and stirred for crystallization. Filter, wash with 20 mL of 40% methanol aqueous solution, and dry at 55°C for 6 hours to obtain 6.001 g of white solid, yield: 85.0%, HPLC purity: 99.6%. The liquid chromatogram of the primary crystallization product is as follows: figure 2 Shown:

[0027] sample catalyst Crude 5-bromo-2-chlorobenzoic acid content Impurity 4-bromo-2-chlor...

Embodiment 2

[0029] Into a 250mL four-neck flask, add 4.7g (0.03mol) of 2-chlorobenzoic acid (0.03mol), concentrated sulfuric acid (40mL), and 0.662g (0.006mol) of potassium sulfide in sequence, stir at 40°C for 20 minutes until the solution is clear, and then add N- Bromosuccinimide 4.271g (0.024mol), continue to react at 40°C for 60 minutes, then slowly pour the solution into 80mL ice-water bath for crystallization to obtain crude 5-bromo-2-chlorobenzoic acid. Add the filter cake to a 250mL four-neck flask, add 24mL of acetic acid and 36mL of water, heat up to 60°C, cool naturally, and stir to crystallize. Filter, wash with 20 mL of 40% acetic acid aqueous solution, and dry at 55°C for 6 hours to obtain 5.973 g of white solid, yield: 84.6%, HPLC purity: 99.7%.

Embodiment 3

[0031] Add 4.700g (0.03mol) of 2-chlorobenzoic acid (0.03mol), concentrated sulfuric acid (40mL), and 2.269g (0.018mol) of sodium sulfite to a 250mL four-necked flask in sequence, stir at 10°C for 20 minutes until the solution is clear, then add N-bromo 3.204 g (0.018 mol) of substituted succinimide was reacted at 10°C for 120 minutes, and then the solution was slowly poured into an 80 mL ice-water bath for crystallization to obtain crude 5-bromo-2-chlorobenzoic acid. Filter, add the filter cake into a 250mL four-neck flask, add 60mL of ethanol, heat up to 60°C, cool naturally, and stir to crystallize. Wash with 20 mL of ethanol solution and dry at 55°C for 6 hours to obtain 5.958 g of white solid, yield: 84.3%, HPLC purity 99.6%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of 5-bromo-2-chlorobenzoic acid and belongs to the technical field of organic synthesis. According to the preparation method, 2-chlorobenzoic acid is takenas a raw material and is subjected to a mono-bromination reaction in an NBS / sulfuric acid system, 5-bromo-2-chlorobenzoic acid is prepared, and a catalyst inhibiting production of 4-bromo-2-chlorobenzoic acid is added in the reaction process. The process is simple, raw materials are cheap and easy to obtain, the cost is low, the yield is high, and the high-purity 5-bromo-2-chlorobenzoic acid product is obtained through one-time refining after the reaction; the catalyst can effectively inhibit production of impurities such as 4-bromo-2-chlorobenzoic acid and the like, and the impurity contentof the obtained product is low.

Description

technical field [0001] The invention relates to a preparation method of 5-bromo-2-chlorobenzoic acid, belonging to the technical field of organic synthesis. Background technique [0002] SGLT-2 inhibitors are a new generation of diabetes drugs. They control blood sugar by inhibiting the reabsorption of glucose in the kidneys. The mechanism of action is unique and does not depend on the abnormality of β cells or the degree of insulin resistance, and the effect will not vary with The failure of β-cell function or the decline of severe insulin resistance will not cause adverse reactions caused by traditional drugs, and has a variety of clinical advantages, especially in clinically showing the advantage of reducing cardiovascular risk. 5-bromo-2-chlorobenzoic acid is a common key intermediate for synthesizing novel antidiabetic drug SGLT-2 inhibitors, and the synthetic method of 5-bromo-2-chlorobenzoic acid in the prior art has the following several kinds: [0003] Starting fro...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/363C07C63/70
CPCC07C51/363C07C63/70
Inventor 刘振强王鹏刘新元梁丙辰王宇栋曹晓倩刘东娜
Owner 河北合佳医药科技集团股份有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com