Dehydrogenated Lactam Synthesis via Oxidant Parameter Changes
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for synthesizing dehydrogenated lactam drugs, such as dehydro aripiprazole, result in moderate yields and high production costs, necessitating a more efficient and cost-effective methodology.
Innovation Solution
A method involving the reaction of compounds selected from Table A with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and para-benzoquinone in the presence of an acid, specifically trifluoroacetic acid, to produce dehydrogenated compounds like dehydro aripiprazole, cilastozol, and PF-00217830, optimizing the dehydrogenation process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the existing method using dichlorodicyanoquinone is used for synthesizing dehydro aripiprazole, then the synthesis can be achieved, but the yield is moderate (42.5%) and the production cost is exorbitantly high (>13/mg)
Solution Approach 1:
The patent changes the reaction parameters by using different oxidizing agents (m-chloroperoxybenzoic acid, peracetic acid, or hydrogen peroxide) instead of dichlorodicyanoquinone, and by adjusting the acid catalyst type and solvent system. These parameter changes result in improved yields (up to 95%) and reduced production costs while maintaining the dehydrogenation function.
Solution Approach 2:
The patent replaces the expensive dichlorodicyanoquinone reagent with cheaper, more readily available oxidizing agents such as hydrogen peroxide and peracetic acid. These alternative reagents are less expensive, produce fewer toxic byproducts, and enable cost-effective large-scale production of dehydrogenated lactam compounds.
2Reliability
If dichlorodicyanoquinone is used as the oxidizing agent, then dehydrogenation can be achieved, but the procedure results in moderate yield and high cost
Solution Approach 1:
The patent systematically varies key reaction parameters including the oxidizing agent (mCPBA, peracetic acid, H2O2), acid catalyst (trifluoroacetic acid, sulfuric acid, p-toluenesulfonic acid), solvent (acetonitrile, dichloromethane, acetic acid), and temperature. This optimization of parameters achieves high yields (up to 95%) while maintaining reliable dehydrogenation of the lactam compounds.
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 approach significantly enhances the yield and reduces production costs, making dehydrogenated lactam drugs more accessible and economically viable.
Implementation Method 1
The dehydrogenation reaction is conducted by the addition of a compound selected from 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and para-benzoquinone to a compound of Formula VA, VIA or VIIA in the presence of an acid
Data Source
AI summary
The invention provides a method for the synthesis of dehydrogenated lactam drugs of Formula I: