Fluralaner Synthesis via Esterification Without Acylation Waste
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The traditional preparation method of fluralaner involves the use of acylation reagents like thionyl chloride or phosphorus trichloride, leading to significant pollution issues due to the generation of waste acid, salt, and other environmental hazards.
Innovation Solution
A method for preparing fluralaner through esterification and ester decomposition-amidation without the need for acylation reagents, using catalysts such as p-toluenesulfonic acid, sulfuric acid, or aluminosilicate molecular sieves, along with alcohols and organic solvents, to produce the esterification solution directly from 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzoic acid and 2-amino-N-(2,2,2-trifluoroethyl)acetamide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If traditional acylation reagents (thionyl chloride, phosphorus trichloride) are used to prepare fluralaner, then the synthesis can proceed, but large amounts of waste acid and salt are generated causing serious pollution
Solution Approach 1:
The patent extracts and eliminates the harmful acylation reagents (thionyl chloride, phosphorus trichloride) from the synthesis process. By removing these problematic reagents that generate waste acid and salt, the method achieves the same synthesis goal without the harmful byproducts, directly addressing the pollution issue while maintaining manufacturing feasibility
Solution Approach 2:
The patent introduces a new intermediary approach using esterification with alcohol and subsequent ester decomposition-amidation. This intermediate ester formation step allows the reaction to proceed without direct acyl chloride formation, thereby avoiding the generation of harmful waste acid and salt while still achieving the target fluralaner product
2Productivity
If acylation reagents are used in the preparation process, then fluralaner can be synthesized, but serious three waster problems (wastewater, exhaust gas, solid waste) occur
Solution Approach 1:
The patent converts the potentially harmful esterification step into a beneficial process. By using esterification with alcohol followed by ester decomposition-amidation, the method transforms what would traditionally be a harmful acylation process into a cleaner synthesis that produces fluralaner without generating the three wasters (wastewater, exhaust gas, solid waste) associated with traditional acylation reagents
3Reliability
If neutralizing waste acid is performed in the traditional method, then the reaction can be completed, but large amounts of salt are produced increasing pollution
Solution Approach 1:
The patent extracts and eliminates the source of waste acid generation by removing the traditional acylation reagents (thionyl chloride, phosphorus trichloride) that produce harmful waste acid. By taking out these reagents from the process, the method achieves reaction completion without generating the waste acid that would otherwise require neutralization and produce large amounts of salt
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method achieves a high yield of fluralaner without generating harmful waste, reducing pollution and ensuring a simple, efficient synthesis process.
Implementation Method 1
subjecting the mixture to esterification to obtain an esterification solution containing 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzoate
Implementation Method 2
subjecting the mixed solution to ester decomposition-amidation to obtain the fluralaner
Implementation Method 3
mixing 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzoic acid, a catalyst, an alcohol and an organic solvent to obtain a mixture
Data Source
AI summary
Provided is a method for preparing fluralaner. The method includes: mixing 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzoic acid, a catalyst, an alcohol and an organic solvent to obtain a mixture, and subjecting the mixture to esterification to obtain an esterification solution containing 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzoate; and mixing the esterification solution with 2-amino-N-(2,2,2-trifluoroethyl)acetamide to obtain a mixed solution and subjecting the mixed solution to ester decomposition-amidation to obtain the fluralaner.