Tetrahydrofuran → 3-(2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one

Participants

Reaction Conditions

Reaction Steps

2.1 g 2-Chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrile were dissolved in a mixture of 20 ml tetrahydrofuran and 20 ml methanol. 3.29 g hydroxylamine hydrochloride were added followed by the addition of 5.74 ml triethylamine. The reaction mixture was stirred at 60° C. overnight. The solvents were removed in vacuo and the resulting residue poured into water and extracted five times with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4 and the solvent was evaporated in vacuo. The residue was dissolved in 10 ml dichloromethane. 0.50 ml pyridine and 0.77 ml phenylchloroformate were added and the mixture stirred at room temperature for fifteen minutes. The mixture was diluted by the addition of 25 ml acetonitrile and 3.54 ml 1,8-diazabicyclo[5.4.0]undec-7-ene were added. The mixture was stirred at room temperature for thirty minutes. The mixture was evaporated in vacuo and the resulting crude material was purified by RP-HPLC to obtain 0.50 g 3-(2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one.

Provenance & Evidence