2-Chlorobenzyl alcohol → ethyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-imidazol-5-yl]-propanoate

Participants

Reaction Steps

To a solution of trifluoromethanesulfonic anhydride (163 μL, 0.966 mmol) in methylene chloride (1 mL) held at -75° C. under argon was added 2-chlorobenzyl alcohol (138 mg, 0.966 mmol) and diisopropylethylamine (168 μL, 0.966 mmol) in methylene chloride (2 mL) over one minute. After being stirred for 15 minutes, a solution of ethyl 3-[2-n-butyl-1-t-butoxycarbonyl-1H-imidazol-4-yl]propanoate (285 mg, 0.878 mmol) in methylene chloride (2 mL) was added over a 3-minute interval at -75° C. The reaction mixture was then allowed to warm to room temperature and was stirred for 18 hours. The solvent was evaporated, and this crude product was flash chromatographed over silica gel with a gradient of ethyl acetate in hexane to give 179 mg (58%) of ethyl 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-1H-imidazol-5-yl]-propanoate as an oil. TLC on silica gel with 1:1 hexane/ethyl acetate showed a single product with an Rf of 0.41.

Provenance & Evidence