Triazole Preparation Process Using Ethanol Solvent
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Solution Overview
Problem
Existing methods for preparing Triazole, a key intermediate for Sitagliptin, suffer from low productivity due to the use of large solvent volumes and complex solvent recovery processes, which increase production costs and environmental impact.
Innovation Solution
A process that converts Amidine to Triazole in an acid environment using ethanol as the sole solvent, reducing solvent volumes and eliminating the need for additional solvents like methanol and MTBE, thereby improving productivity and reducing waste.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If large volumes of solvents (methanol, water, MTBE) are used for Triazole preparation and isolation, then the reaction can proceed and product can be isolated, but productivity decreases and solvent recovery becomes complex and time-consuming
Solution Approach 1:
The patent changes the solvent system from a multi-component mixture (methanol-water-MTBE) to a single-component system (ethanol). This parameter change simplifies the solvent composition, enabling both the reaction and isolation to be performed in the same solvent, thereby reducing solvent recovery complexity and time while maintaining or improving productivity
Solution Approach 2:
Ethanol serves multiple functions in this invention: it acts as the reaction solvent for the conversion of amidine to triazole, and simultaneously serves as the isolation solvent for product precipitation. This multi-functionality eliminates the need for separate solvent systems for reaction and isolation, reducing overall solvent volume and recovery time
2Productivity
If multiple solvents (methanol, water, MTBE) are used for conversion and isolation, then the process can be completed, but the complexity of the process increases and productivity decreases
Solution Approach 1:
The patent merges the reaction solvent function and isolation solvent function into a single solvent system (ethanol). Previously, different solvents were used for reaction (methanol-water) and isolation (MTBE), but now both functions are accomplished in ethanol, simplifying the overall process and reducing complexity
Solution Approach 2:
The invention changes the solvent composition parameter from a complex multi-solvent system to a simple single-solvent system. This parameter simplification reduces process complexity while maintaining effective conversion and isolation capabilities, thereby improving productivity
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
The process significantly increases productivity with a molar yield of 89.00% to 90.70% and HPLC purity over 99.7%, while minimizing solvent usage and costs, and simplifying the isolation process.
Implementation Method 1
the synthesis of [1,2,4]Triazolo[4,3-r]piperazines via condensation of high reactive chloromethyloxadiazoles with ethylenediamins
Implementation Method 2
the conversion is carried out in ethanol, only
Implementation Method 3
from thus obtained suspension of compound (II) in ethanol, the product of formula (II) is isolated
Data Source
AI summary
Object of the present invention is an improved process for the preparation of Triazole of formula (II) and salt thereof, a key intermediate for the synthesis of Sitagliptine.