Synthesis 2016; 48(22): 3996-4008
DOI: 10.1055/s-0035-1561464
paper
© Georg Thieme Verlag Stuttgart · New York

Alkyl Nitrites: Novel Reagents for One-Pot Synthesis of 3,5-Disubstituted Isoxazoles from Aldoximes and Alkynes

Kishorkumar S. Kadam
a  Department of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India
,
Thirumanavelan Gandhi*
b  Department of Chemistry, School of Advanced Sciences, VIT University, Vellore 632014, Tamil Nadu, India   Email: [email protected]
,
Amol Gupte
a  Department of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India
,
A. K. Gangopadhyay
a  Department of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India
,
Rajiv Sharma
a  Department of Medicinal Chemistry, Piramal Enterprises Limited, Goregaon (E), Mumbai 400063, Maharashtra, India
› Author Affiliations
Further Information

Publication History

Received: 18 March 2016

Accepted after revision: 29 April 2016

Publication Date:
22 June 2016 (online)


Abstract

An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert-butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor.

Supporting Information

 
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