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

Synthetic method of fluralana

A technique for the synthesis of frellaner and a synthetic method, which is applied in the field of frellaner synthesis, can solve the problems of high economic cost, low yield, long reaction time, etc., so as to improve economic benefits, reduce production costs, and reduce reagent consumption Effect

Pending Publication Date: 2022-04-12
JIANGSU TIANHE PHARMA CO LTD
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] CN109879826, CN111675667, and CN112457267 all mentioned that 4-formyl-2-methylbenzoic acid was used as a raw material, through oximation, substitution, condensation, and ring-closing reaction to obtain Freylana, but in the key step, in the ring-closing reaction, There is a problem of low yield
[0007] In addition, the existing synthesis process also includes using 4-bromo-2-methylbenzoic acid as raw material to obtain 4-acetyl-2-methylbenzoic acid through Suzuki coupling reaction, and then undergo condensation and dehydration ring closure to prepare fluorine Leilana, but there are problems such as high economic cost and long response time

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
  • Synthetic method of fluralana
  • Synthetic method of fluralana
  • Synthetic method of fluralana

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Embodiment 1: Preparation of 4-acetyl-2-methylbenzoic acid (intermediate 1)

[0042]

[0043] 4-Bromo-2-methyl-benzoic acid (compound 0) (0.277g, 1.29mmol), n-butyl vinyl ether (0.83ml, 6.42mmol), 1,3-bis(diphenylphosphine)propane (0.17g, 0.04mmol), palladium acetate (0.0023g, 0.01mmol), potassium carbonate (0.3g, 2.17mmol) were added to the bottle, 10mL of n-butanol was added, nitrogen was replaced 3 times, and the heating temperature was controlled to reflux at 90°C After 9 to 10 hours, the reaction of the raw materials is complete, stop heating, cool to room temperature, add water and concentrated hydrochloric acid to adjust the pH to 1-2, extract with ethyl acetate, wash the organic phase with water in turn, wash with saturated aqueous sodium chloride solution, and diatomaceous earth After filtration, it was dried over anhydrous sodium sulfate and spin-dried. 0.263 g of compound 1 was obtained as a yellow solid with a yield of 95%. 1 HNMR (300MHz, CDCl 3 )δ8.1...

Embodiment 2

[0044] Example 2: Preparation of 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutyl)-benzoic acid (intermediate 3)

[0045]

[0046] Compound 1 (0.5g, 2.8mmol), compound 2 (0.68g, 2.8mmol), sodium lauricate (0.04g, 0.18mmol), potassium carbonate (0.6g, 4.34mmol), water (12mL, 0.66mol) Mix well, and stir at 60°C for 24 hours. At this time, the reactant becomes slightly white mud. Add water to the reaction liquid, adjust the pH to 1-2 with concentrated hydrochloric acid, extract with ethyl acetate, dry with anhydrous sodium sulfate, and purify by column chromatography. , the mobile phase was petroleum ether (PE) and ethyl acetate (EA), (PE:ethyl acetate EA=2:1, v:v), and 0.915g of a yellowish solid was obtained with a yield of 77.42%.

[0047] 1 HNMR (300MHz, CDCl 3 )δ8.21(d, J=8.3Hz, 1H), 7.87(d, J=7.5Hz, 2H), 7.55(d, J=1.8Hz, 2H), 7.41(d, J=1.8Hz, 1H) ,5.64(s,1H),3.92(d,J=17.6Hz,1H),3.76(d,J=17.6Hz,1H),2.78(s,3H).

Embodiment 3

[0048] Example 3: (1) Preparation of 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-2-enol)-benzoic acid (intermediate 4)

[0049]

[0050] Compound 3 (0.5g, 1.19mmol) was dissolved in 20mL of dichloromethane, and triethylamine (0.62g, 6.12mmol) was added under stirring to react at room temperature for 1h, and then the reaction solution was spin-dried to obtain triethylamine salt. Add 20mL of toluene and 4-dimethylaminopyridine (0.03g, 0.24mmol) to the ethylamine salt and heat to 60°C, add acetic anhydride (0.4mL, 4.2mmol) dropwise, after the addition is complete, heat up to 80°C , stirred for 6 hours, monitored for complete reaction, cooled to room temperature, added water, adjusted the pH to 1-2 with concentrated hydrochloric acid, extracted with EA, washed with water, washed with salt, dried over anhydrous sodium sulfate, and obtained 0.405 g of a yellow solid. The yield was 84.6%, and the next step was prepared.

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

According to the method, 2-methyl-5-bromobenzoic acid is adopted as a raw material, and Suzuki coupling reaction, condensation reaction, dehydration cyclization reaction and amide condensation reaction are performed to finally obtain the fluralan. According to the synthesis method, the reaction cost is reduced, the yield is improved, and the reaction period is shortened.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a synthesis method of Freilaner. Background technique [0002] Frellana is a broad-spectrum insecticide of the isoxazoline class. It has been registered and marketed as a veterinary drug, and its trade name is BRAVECTO TM [1]. The CAS number of Frellaner is 864731-61-3, and the CAS name is 4-[5-(3,5-difluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3 -Isoxazolyl]-2-methyl-sense[2-oxo-2-[(2,2,2-trifluoroethyl)oxy]ethyl]benzamide, the Chinese common name is Fluorine Lana. Its chemical structural formula is as follows: [0003] [0004] Freilaner is mainly used for the treatment of animal parasites. It is similar to the targets of insecticides such as phenylpyrazoles, cyclopentadienes, and macrolides. It belongs to the γ-aminobutyric acid-gated chloride ion Channel disruptor, its mechanism of action is mainly to achieve the insecticidal effect by inter...

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): C07D261/04
Inventor 戴振亚何敬杰解妍徐佳伟赵云德
Owner JIANGSU TIANHE PHARMA 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