Ammonium Chloride → (2-Methyl-1-trityl-1H-imidazol-4-YL)(1-(trifluoromethyl)cyclopropyl)methanone

Participants

Reaction Conditions

Reaction Steps

Ethylmagnesium bromide (3 M solution in diethyl ether) (633 mL, 1.9 mol) was added over 1 h to a 5° C. solution of 4-iodo-2-methyl-1-trityl-1H-imidazole (855 g, 1.9 mol) in methylene chloride (8 L). After stirring at 5° C. for 30 min, the reaction mixture was allowed to warm to ca. 12° C. and a solution of N-methoxy-N-methyl-1-(trifluoromethyl)cyclopropanecarboxamide (355 g, 1.8 mol) in methylene chloride (2 L) was added over 1 h. After stirring at ambient temperature overnight, the reaction mixture was poured into saturated aqueous ammonium chloride. The organic phase was washed with saturated aqueous sodium bicarbonate, dried (magnesium sulfate) and concentrated in vacuo. The residue was dissolved in a minimal volume of ether and crashed out with heptane. After stirring in heptane (ca. 3 L) for 1 h, solid was collected by filtration, washing with heptane to afford (2-methyl-1-trityl-1H-imidazol-4-yl)[1-(trifluoromethyl)cyclopropyl]methanone.

Provenance & Evidence