Dimethylformamide → 3-[4-(2-Trifluoromethylsulfanyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide

Participants

Reaction Steps

3-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 2; 60 mg, 0.30 mmol) was dissolved in THF (1.5 mL). K2CO3 (41 mg, 0.30 mmol) and tetrabutylammonium iodide (15 mg, 0.04 mmol) were added. 2-(Trifluoromethylthio)benzyl bromide (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA; 88 μL, 0.30 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 h. DMF (100 μL) was added and the mixture was heated at 45° C. for 4 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (5 mL) and H2O (5 mL). The organic layer was evaporated and the residue was purified by chromatography (35-50% EtOAc/hexanes) to give 3-[4-(2-trifluoromethylsulfanyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (60 mg, 52%) as a white solid. HRMS Calcd. for C18H14F3N2O3S (M+H)+, 395.0672. Found: 395.0688.

Provenance & Evidence