Ammonium Acetate → 4-[1-Hydroxy-5-(2-methylthiopyrimidin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

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Reaction Steps

To a mixture of 1-(2-methylthiopyrimidin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime (5.0 g, 0.0146 mole) and N-carbobenzyloxypiperidine-4-carboxaldehyde [Amici et al Eur. J. Med. Chem. 26, 625-631 (1991)] (4.70 g, 0.019 mole), in acetic acid (140 mL) was added ammonium acetate (23 g, 0.295 mole). The mixture was heated to reflux for 11/2 hours, cooled and concentrated to remove most of the acetic acid. The residue was dissolved in water (200 mL) and ethyl acetate (400 mL) and the pH adjusted to 7.5 with 3N sodium hydroxide. The ethyl acetate layer was removed, dried over Na2SO4, filtered and concentrated to give an oil (9.5 g crude product). The oil was used in the next step without further purification.

Provenance & Evidence