1 Department of Chemistry and Biochemistry, Concordia University 7141 rue Sherbrooke O. Montréal QC Canada H4B 1R6 pat.forgione@concordia.ca.
2 Centre for Green Chemistry and Catalysis, McGill University 801 rue Sherbrooke O. Montréal QC Canada H3A 0B8.

Scalable, solvent-free synthesis of 3,5-isoxazoles under ball-milling conditions has been developed. The proposed methodology allows the synthesis of 3,5-isoxazoles in moderate to excellent yields from terminal alkynes and hydroxyimidoyl chlorides, using a recyclable Cu/Al₂O₃ nanocomposite catalyst. Furthermore, the proposed conditions are reproducible to a 1.0-gram scale without further milling time variations.