10.1021/op100251q
The study presents the development of a second-generation synthetic process for eletriptan, a drug used to treat migraines, employing a Fischer indole cyclization approach. The new process aims to overcome the limitations of the existing manufacturing route, which includes the use of expensive and harmful starting materials, and generates significant waste. The research details the synthesis of key intermediates, such as aldehyde 8 and hydrazine 10, and explores various methods to improve yield and scalability. The study also discusses the successful application of the Fischer indole reaction to synthesize eletriptan and the optimization of the process using L-ascorbic acid for the reduction of diazonium salts to aryl hydrazines, resulting in a more cost-effective, efficient, and environmentally friendly synthesis route. The final objective was achieved by synthesizing the single enantiomer of eletriptan (R)-7 through classical resolution techniques, offering a potentially more sustainable and scalable method for its production.
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