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

Synthesis method of dapagliflozin midbody 5-bromine-2-chloro-benzoyl chloride

The technology of a kind of chlorobenzoyl chloride and synthesis method is applied in the field of synthesis of dapagliflozin intermediate 5-bromo-2-chlorobenzoyl chloride, which can solve the problems of three wastes pollution and unsafe operation, and achieve less side reactions, The effect of safe operation and low process cost

Inactive Publication Date: 2019-03-12
THE SECOND PEOPLES HOSPITAL OF SHENZHEN
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the prior art, the synthesis of 5-bromo-2-chlorobenzoyl chloride is generally obtained by chlorination reactions such as 5-bromo-2-chlorobenzoic acid and thionyl chloride, phosphorus trichloride, and using these reagents often brings Unsafe operation, three waste pollution and other issues

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
  • Synthesis method of dapagliflozin midbody 5-bromine-2-chloro-benzoyl chloride
  • Synthesis method of dapagliflozin midbody 5-bromine-2-chloro-benzoyl chloride
  • Synthesis method of dapagliflozin midbody 5-bromine-2-chloro-benzoyl chloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The synthetic method of 5-bromo-2-chlorobenzoyl chloride comprises the following steps:

[0033] 1) Mix monomethyl oxalyl chloride and 1,1,1-trichloroethane, add the catalyst, stir and pass in argon, control the pressure to 6 atmospheres, control the temperature to 125°C, maintain for 1.5h, and then First add the solution of 4-bromochlorobenzene and chloroform dropwise. After the addition is complete, the temperature of the system is raised to 165° C., and the pressure is raised to 8 atmospheres to continue the reaction for 14 hours.

[0034] The catalyst is obtained by the following method: grind 4A molecular sieves, pass through 350 meshes, soak for 4 days in 12% copper sulfate aqueous solution, filter, and activate at 400°C; the weight ratio of molecular sieves to copper sulfate aqueous solution is 1:7.2.

[0035] The molar ratio of 4-bromochlorobenzene to monomethyl oxalyl chloride is 1:1.12; the dosage ratio of monomethyl oxalyl chloride to 1,1,1-trichloroethane i...

Embodiment 2

[0038] The synthetic method of 5-bromo-2-chlorobenzoyl chloride comprises the following steps:

[0039] 1) Mix allyl oxalyl chloride monoallyl with carbon tetrachloride, add the catalyst, stir and feed nitrogen, control the pressure to 4 atmospheres, control the temperature to 110 ° C, keep it for 1 hour, and then add 4-bromochloro After adding the solution of benzene and 1,2-dichloroethane, the temperature of the system was raised to 150°C, and the pressure was raised to 5 atmospheres to continue the reaction. 10 End.

[0040] The catalyst is obtained by the following method: grind 5A molecular sieves, pass through 200 meshes, soak in 10% copper sulfate aqueous solution for 2 days, filter, and bake and activate at 300°C; the weight ratio of molecular sieves to copper sulfate aqueous solution is 1:5.

[0041] The molar ratio of 4-bromochlorobenzene to monoallyl oxalyl chloride is 1:1.05; the dosage ratio of monoallyl oxalyl chloride to carbon tetrachloride is 1g:8ml; 4-bromoc...

Embodiment 3

[0044] The synthetic method of 5-bromo-2-chlorobenzoyl chloride comprises the following steps:

[0045] 1) Mix ethyl oxalyl chloride and 1,1,1-trichloroethane evenly, add catalyst, stir and pass protective gas, control the pressure to 7 atmospheres, control the temperature to 136°C, keep it for 2 hours, and then drop it first After adding a solution of 4-bromochlorobenzene and chloroform, the temperature of the system was raised to 170° C., and the pressure was increased to 9 atmospheres to continue the reaction for 16 hours.

[0046] The catalyst is obtained by the following method: grind the 4A type molecular sieve, pass through 400 meshes, soak in 15% copper sulfate aqueous solution for 5 days, filter, and bake and activate at 450°C; the weight ratio of molecular sieve to copper sulfate aqueous solution is 1:8.

[0047] The molar ratio of 4-bromochlorobenzene to ethyl oxalyl chloride is 1:1.15; the amount ratio of ethyl oxalyl chloride to 1,1,1-trichloroethane is 1g:12ml; ...

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 synthesis method of dapagliflozin midbody 5-bromine-2-chloro-benzoyl chloride. The synthesis method comprises the following steps that (1) ethyl oxalyl monochloride is blended uniformly with a solvent A, a catalyst is added and stirred, protection air is guided in, the pressure is controlled to be 4-7 barometric pressure, the temperature is controlled to be 110-136 DEG C,the pressure and the temperature are maintained for 1-2 h, a solution of 4-bromochlorobenzene and a solvent B is added dropwise, after adding is completed, the system is heated to be at the temperature of 150-170 DEG C, the pressure is increased to be 5-9 barometric pressure, and the reaction is continued for 10-16 h and stopped; and (2) the solid is filtered and removed after the product is cooled, the filtrate is added into a solvent C with the volume being 1-2 times of the filtrate, washing is conducted till the pH value is 7, the mixture is dried by using a desiccant, all the solvents areevaporated and removed, and the product is obtained. The synthesis method is high in yield, and no harmful substance is discharged.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a method for synthesizing dapagliflozin intermediate 5-bromo-2-chlorobenzoyl chloride. Background technique [0002] Dapagliflozin (1), chemical name: (2S,3R,4R,5S,6R)-2-3-[4-ethoxybenzyl)-4-chlorophenyl]-6-hydroxy Methyltetrahydro-2H-pyran-3,4,5-triol [c], whose chemical structure is shown below: [0003] [0004] Dapagliflozin is a reversible and highly selective hypoglycemic drug named Farxiga jointly developed by Bristol-Myers Squibb and AstraZeneca in the United States. It was approved by the European Medicines Agency (EMA) in 2012. In January 2014, the FDA approved its marketing. Diabetes has a wide range of diseases and a large number of patients. At present, although there are many drugs for the treatment of diabetes, there is no completely satisfactory drug so far. SGLT2 inhibitors, these inhibitors are newly developed drugs in recent years, and their targets ar...

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): C07C63/70C07C51/62B01J29/76
CPCB01J29/7607B01J2229/186C07C51/62C07C63/70
Inventor 谭回李维平黄贤键唐爱发刘文兰陈垒
Owner THE SECOND PEOPLES HOSPITAL OF SHENZHEN
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com