Convenient Approach to 3,4-Diarylisoxazoles Based on the Suzuki Cross-Coupling Reaction

✍ Scribed by J. S. Dileep Kumar; ManKit M. Ho; Jennifer M. Leung; Tatsushi Toyokuni

• Book ID: 101391884
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 89 KB
• Volume: 344
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/1615-4169(200212)344:10<1146::aid-adsc1146>3.0.co;2-1

✦ Synopsis

The Suzuki cross-coupling reaction was found effective for rapid access to a series of 3,4diarylisoxazoles of pharmacological interest. The efficiency of this approach was demonstrated by the synthesis of the highly potent COX-2-selective inhibitor, 4-(5-methyl-3-phenyl-4-isoxazolyl)benzenesulfonamide (valdecoxib), and its analogues. Thus, the coupling reaction between (3-aryl-5-methyl-4isoxazolyl)boronic acids, prepared in situ from the corresponding bromides using triisopropyl borate, and aryl bromides containing a 4-sulfonamide or 4methylsulfonyl group under the standard conditions [Pd(PPh 3 ) 4 , Na 2 CO 3 , EtOH-H 2 O, reflux] yielded the target 3,4-diarylisoxazoles in good yields.