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

Preparation method of trimethoprim midbody 3,5-dibromo-4-hydroxy benzaldehyde

A technology of hydroxybenzaldehyde and trimethoprim, which is applied in the field of preparation of trimethoprim intermediate 3,5-dibromo-4-hydroxybenzaldehyde, can solve the cumbersome preparation process, strong bromine toxicity, and short reaction time Long and other problems, to achieve the effect of simple process, fast reaction speed and mild reaction conditions

Active Publication Date: 2015-12-02
ZHEJIANG ESIGMA BIOTECH CO LTD
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation process is cumbersome, the reaction time is long, and the bromine used is extremely toxic, and the product yield is only 84%.

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 trimethoprim midbody 3,5-dibromo-4-hydroxy benzaldehyde

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Add 10.8g (0.1mol) of p-cresol, 48.6g of acetic acid, and 0.68g (0.005mol) of zinc chloride into the three-necked flask, stir, cool down to 0°C and slowly add BTMABr 3 156g (0.4mol), react at 10°C for 1 hour, then raise the temperature to 90°C for 1.5 hours.

[0022] After the reaction was completed, acetic acid was recovered by distillation under reduced pressure, the substrate was stirred with 70ml of water, heated and refluxed for 4 hours, cooled to room temperature, filtered, washed with water, and dried to obtain 26.40g of 3,5-dibromo-4-hydroxybenzaldehyde, HPLC purity It was 98.75%, and the yield was 93.11%.

Embodiment 2

[0024] Add 10.8g (0.1mol) of p-cresol, 54g of acetic acid, 0.68g (0.005mol) of zinc chloride into the three-necked flask, stir, cool down to 0°C and slowly add BTMABr 3 175.5g (0.45mol), reacted at 15°C for 2 hours, then raised the temperature to 95°C for 3 hours.

[0025] After the reaction was completed, acetic acid was recovered by distillation under reduced pressure, the substrate was stirred with 70ml of water, heated and refluxed for 2 hours, cooled to room temperature, filtered, washed with water, and dried to obtain 26.74g of 3,5-dibromo-4-hydroxybenzaldehyde, HPLC purity It is 98.09%, and the yield is 93.68%.

Embodiment 3

[0027] Add 10.8g (0.1mol) of p-cresol, 54g of acetic acid, 0.68g (0.005mol) of zinc chloride into the three-necked flask, stir, cool down to 0°C and slowly add BTMABr 3 159.9 g (0.41 mol), react at 12°C for 1.5 hours, then raise the temperature to 92°C for 2 hours.

[0028] After the reaction was completed, acetic acid was recovered by distillation under reduced pressure, the substrate was stirred with 70ml of water, heated and refluxed for 3 hours, cooled to room temperature, filtered, washed with water, and dried to obtain 26.49g of 3,5-dibromo-4-hydroxybenzaldehyde, HPLC purity It is 99.22%, and the yield is 93.86%.

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 provides a preparation method of trimethoprim midbody 3,5-dibromo-4-hydroxy benzaldehyde. The preparation method comprises the following steps of sequentially adding paracresol, ethanoic acid and zinc chloride in a reaction container; uniformly stirring; slowly adding benzyl trimethyl ammonium tribromide after cooling to the temperature of 0 DEG C; reacting for 1-2 hours at the temperature of 10-15 DEG C; heating to the temperature of 90-95 DEG C and reacting for 1.5-3 hours; performing reduced pressure distillation on reaction liquid to recycle acetic acid; adding water in a substrate, stirring, heating and performing backflow hydrolysis for 2-4 hours; cooling to room temperature; and filtering, washing and drying to obtain the 3,5-dibromo-4-hydroxy benzaldehyde. Reaction conditions of the preparation method are gentle, a technology is simple, reaction speed is high, the purity of products is above 98%, yield is above 93%, and BTMABr3 serves as a bromination reagent and replaces bromine with high toxicity. The preparation method has the advantages of safety, zero toxicity and environmental protection.

Description

technical field [0001] The invention belongs to the technical field of veterinary drug preparation, and in particular relates to a preparation method of a trimethoprim intermediate 3,5-dibromo-4-hydroxybenzaldehyde. Background technique [0002] Trimethoprim is a white or off-white crystalline powder. It is a broad-spectrum, high-efficiency, low-toxic antibacterial and fungicide, and its antibacterial spectrum is similar to that of sulfonamides. In the early 1960s, it was found that it can greatly enhance the effectiveness of sulfa drugs, so it is called sulfa synergist. At present, the drug is widely used in compound sulfonamide preparations, becoming one of the most widely used drugs. Trimethoprim can inhibit dihydrofolate reductase, and sulfonamides can inhibit dihydrofolate synthase. Due to the similar in vivo process and pharmacodynamic characteristics of the two, the combined drug can simultaneously block the two consecutive steps of the nucleic acid and protein synt...

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): C07C47/565C07C45/43
CPCC07C37/62C07C45/43C07C39/27C07C39/26C07C47/565
Inventor 吴中华张小朋陈贵才徐天华
Owner ZHEJIANG ESIGMA BIOTECH CO LTD
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