Optimization of reaction conditions of 1a with NH₂OH·HCl to access 4,5-disubstituted isoxazoles regioisomers 2a and 3a regioselectively^a.

Entry	i			Ratiob (%)		Yieldc (%)
	Solvent	Base	Time (h)/Temp. (°C)	2a	3a
1	EtOH	—	10/25	35	65	73
2	MeCN	—	16/25	65	35	81
3	EtOH/H2O	—	10/25	40	60	68
4	EtOH	Py	2/25	64	36	71
5	MeCN	Py	2/25	76	24	87
6	MeCN	DBU	2/25	—d		—
7	MeCN	K2CO3	2/25	—d		—
8	EtOH	—	1/reflux	23	77	76
9	MeCN	—	3/reflux	54	46	78
10	MeCN	Py	1/reflux	45	55	80
11	EtOH	Py	1/reflux	62	38	74

^aReaction conditions: 1a (0.5 mmol), NH₂OH·HCl (0.6 mmol, 1.2 equiv.), base (0.6 mmol, 1.2 equiv.), solvent (4 mL).

^bCalculated from the ¹H-NMR spectrum of crude product.

^cIsolated yield (regioisomeric mixture).

^d2a and 3a as intractable mixtures of several products.