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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Piperazine amide linker for cyclative cleavage from solid support: traceless synthesis of dihydroquinoxalin-2-ones
Cleopatra Neagoie1, Viktor Krchňák
1Department of Organic Chemistry, Faculty of Science, Palacký University , 17. Listopadu 12, 771 46 Olomouc, Czech Republic.
Abstract:
A piperazine amide linker for cyclative cleavage from solid support and its use in the traceless solid-phase synthesis of dihydroquinoxalinones are described. Piperazine was attached to Wang resin via a carbamate linkage and acylated with Fmoc-amino acids. Following Fmoc group removal, resin-bound amines were reacted with 1-fluoro-2-nitrobenzenes. The nitro group of the resulting 2-nitroanilines was reduced, and acyclic precursors, in contrast to traditional ester-type linkage, remained attached to the resin. Target dihydroquinoxalinones were obtained either by acid- or microwave-mediated cyclative cleavage. The synthesis provided crude compounds of high purity and enabled the preparation of stable immobilized linear intermediates. The linker is suitable for combinatorial synthesis of compound libraries.
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