Solid-Phase Synthesis of 5-Isoxazol-4-yl-[1,2,4]oxadiazoles

Chao Quan, Mark Kurth

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A library of isoxazole and 1,2,4-oxadiazole-containing diheterocyclic compounds has been prepared. Our strategy was explored in solution phase first as follows. PMB-protected 3-butyn-2-ol was deprotonated with nBuLi, acylated with methyl chloroformate, and then employed in a nitrile oxide 1,3-dipolar cycloaddition (benzaldehyde oxime in the presence of bleach) to afford the isoxazole-substituted carboxylic acid methyl ester. Ester saponification with aqueous NaOH followed by a two-step condensation with benzamidoxime gave the final isoxazole-oxadiazole diheterocyclic product in good yield. With some modifications, we next explored this chemistry on Wang resin, which led to 18 final products that were cleaved from polymer beads with 50% TFA in dichloromethane.

Original languageEnglish (US)
Pages (from-to)1470-1474
Number of pages5
JournalJournal of Organic Chemistry
Volume69
Issue number5
DOIs
StatePublished - Mar 5 2004

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Oxadiazoles
Isoxazoles
Esters
Saponification
Nitriles
Oximes
Cycloaddition
Methylene Chloride
Carboxylic Acids
Oxides
Condensation
Polymers
azastene

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Solid-Phase Synthesis of 5-Isoxazol-4-yl-[1,2,4]oxadiazoles. / Quan, Chao; Kurth, Mark.

In: Journal of Organic Chemistry, Vol. 69, No. 5, 05.03.2004, p. 1470-1474.

Research output: Contribution to journalArticle

Quan, Chao ; Kurth, Mark. / Solid-Phase Synthesis of 5-Isoxazol-4-yl-[1,2,4]oxadiazoles. In: Journal of Organic Chemistry. 2004 ; Vol. 69, No. 5. pp. 1470-1474.
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