Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of 4-(bromoacetyl) pyridine hydrobromide

A technology of pyridine hydrobromide and acetylpyridine, which is applied in the field of preparation of ceftaroline axetil intermediate 4-(bromoacetyl)pyridine hydrobromide, can solve the problems of unfavorable health of operators, high pressure on environmental protection, Unfavorable production and other problems, to achieve the effect of saving raw material costs and production costs, reducing the requirements for production equipment, and saving raw material costs

Inactive Publication Date: 2017-05-10
山东诚汇双达药业有限公司
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] (1) Bromine has a pungent smell and strong corrosiveness; and it is highly toxic, which is not conducive to safe production operations and is not conducive to the health of operators
[0007] (2) Although bromine and the substrate react in equimolar amounts, half of hydrogen bromide is actually produced, which is not suitable for large-scale production because of the high pressure on environmental protection
[0008] (3) The reaction efficiency can be improved by using HBr / HOAc solution, but a mixed solution of hydrobromic acid and acetic acid is introduced, and the generated waste liquid needs to be treated in an environmentally friendly manner, which is not conducive to safe and environmentally friendly production
[0009] (4) The freezing point of glacial acetic acid is 16.7°C, and it is easy to crystallize and precipitate when the temperature is low, which is not conducive to production when the temperature is low
[0010] (5) Excess bromine and the introduction of HBr / HOAc solution in the reaction greatly increase the raw material cost and environmental protection cost of producing 4-(bromoacetyl)pyridine hydrobromide
[0011] (6) The ether used in the post-reaction treatment has a lower boiling point slightly higher than normal temperature, which is difficult to transport and unsafe to operate in industrial production, and the recovery rate is far lower than 40%.

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Add 600g of ethyl acetate and 121.1g of 4-acetylpyridine into the reaction flask, stir well and then add 186.9g of NBS in batches at 20~30°C; after the addition, slowly raise the temperature to 60~70°C, and monitor the raw material reaction for 10 hours to complete , cooled to 10~20°C for full crystallization. Filter, beat and wash with 550g of deionized water, filter again, and dry to obtain 270.8g of off-white 4-(bromoacetyl)pyridine hydrobromide, with a molar yield of 96.5% and a melting point of 194-195°C.

Embodiment 2

[0035] Add 720g of ethyl acetate and 121.1g of 4-acetylpyridine into the reaction flask, stir well and then add 195.8g of NBS in batches at 20~30°C; after the addition, slowly raise the temperature to 50~60°C, and monitor the raw material reaction for 10 hours to complete , cooled to 10~20°C for full crystallization. Filter, beat and wash with 600g of deionized water, filter again, and dry to obtain 272.6g of off-white 4-(bromoacetyl)pyridine hydrobromide, with a molar yield of 97.0% and a melting point of 194-195°C.

Embodiment 3

[0037] Add 600g of ethyl acetate and 121.1g of 4-acetylpyridine into the reaction flask, stir well and then add 186.9g of NBS in batches at 20~30°C; after the addition, slowly raise the temperature to 65~75°C, and monitor the raw material reaction for 8 hours to complete , cooled to 0~10°C for full crystallization. Filter, beat and wash with 650g of deionized water, filter again, and dry to obtain 274.2g of off-white 4-(bromoacetyl)pyridine hydrobromide, with a molar yield of 97.6% and a melting point of 194-195°C. The mother liquor 545g of ethyl acetate can be directly applied to the next batch of production without treatment.

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 relates to the technical field of synthesis of medical intermediates, in particular to a preparation method of 4-(bromoacetyl) pyridine hydrobromide of a ceftaroline fosamil intermediate. The method comprises the following steps that 4-acetyl pyridine is used as a raw material, ester is used as a solvent and NBS serves as a bromination reagent to obtain the 4-(bromoacetyl) pyridine hydrobromide through reaction. The preparation method is mild in reaction condition, high in yield, high in safety, green, environmentally friendly, low in cost and suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of synthesis of pharmaceutical intermediates, in particular to a preparation method of ceftaroline axetil intermediate 4-(bromoacetyl)pyridine hydrobromide. Background technique [0002] 4-(Bromoacetyl)pyridine hydrobromide is a key intermediate in the synthesis of ceftaroline axetil, CAS No. 5349-17-7, molecular formula C 7 h 7 Br 2 NO, the structural formula is as follows: [0003] . [0004] On October 29, 2010, Forest Laboratories announced that its "fifth generation" cephalosporin antibiotic ceftaroline axetil (trade name Teflaro) was approved by the US FDA for the treatment of community-acquired bacterial pneumonia and acute bacterial pneumonia. Skin and skin tissue infections, including infections caused by methicillin-resistant Staphylococcus aureus. 4-(Bromoacetyl)pyridine hydrobromide, as the key intermediate of ceftaroline axetil, directly affects the production, market supply and quality o...

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
IPC IPC(8): C07D213/50
CPCC07D213/50
Inventor 李跃东宋希军刘增强张伟谭光明
Owner 山东诚汇双达药业有限公司
Features
  • R&D
  • 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