Scheme 1. General Synthetic Route of Biarylether Sulfonamides Exemplified with Benzisoxazole 3.

Reagents and conditions: (a) N-hydroxyacetamide, t-BuOK, DMF, 99%; (b) TFA, conc. HCl, reflux, 93%; (c) di-tert-butyl dicarbonate, DMAP, CH₂Cl₂, 58%; (d) (5-chloro-2-hydroxyphenyl)boronic acid, Pd(PPh₃)₄, Na₂CO₃ (2 M), DME, reflux, 63%; (e) 9, K₂CO₃, DMSO, 55%; (f) TFA, CH₂Cl₂, 63%; (g) NaOH, MeOH, 96%. (h) (1) 2,4-dimethoxybenzaldehyde, toluene, Dean–Stark, reflux, (2) NaBH₄, MeOH, 59%; (i) 2,4,5-trifluorobenzenesulfonyl chloride, LiN(TMS)₂, THF, −78 °C, 84%.