Hydrochloric Acid → (1-methyl-1H-tetrazol-5-yl)[3-(trifluoromethoxy)phenyl]methanone

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-methyl-1H-tetrazole (7.68 g, 91.3 mmol) in anhydrous THF (360 mL), cooled to −70° C. with an acetone/dry ice bath, was added dropwise a solution of n-butyllithium (1.6 M in hexanes, 57.1 mL, 91.3 mmol). After the addition was over, the resulting cloudy suspension was stirred for 45 min at −70° C. A solution of N-methoxy-N-methyl-3-(trifluoromethoxy)benzamide (22.3 g, 76.1 mmol) in THF (60 mL) was then added dropwise while keeping the internal temperature below −60° C. The reaction mixture was then allowed to warm up and stirred at room temperature for 18 h. The reaction mixture was poured into a mixture of ice-cold water (100 mL) and aq. HCl (1 M, 100 mL), the layers were separated, the water phase was extracted with ethyl acetate (2×150 mL), the combined organic layers were washed with water (2×200 mL) and dried (MgSO4). Purification on silica gel afforded (1-methyl-1H-tetrazol-5-yl)[3-(trifluoromethoxy)phenyl]methanone as a light yellow oil [5.12 g, yield 21%; HPLC/MS:m/z=273 (M+H); log P(HCOOH)=2.96].

Provenance & Evidence