Dimethyl Sulfoxide → HCID 15399109, compound

Participants

Reaction Conditions

Reaction Steps

Oxalyl chloride (0.34 mL, 3.9 mmol) was added to a solution of dimethyl sulfoxide (0.41 mL, 5.8 mmol) in methylene chloride (10 mL) at −78° C. After 20 min. at −78° C., 3-(benzyloxycarbonyl-amino)-N-[1-(2-fluoro-pyridin4-yl)-2-hydroxy-2-(3-trifluoromethyl-phenyl)ethyl]-N-methyl-propionamide (1.0 g, 1.9 mmol) in methylene chloride (10 mL) was added and the reaction solution was stirred at −78° C. for 2 hrs. Triethylamine (1.3 mL, 9.6 mmol) was added and the cooling bath was removed. The solution was diluted with ethyl acetate (150 mL), washed with aqueous ammonium chloride (75 mL) and brine (75 mL), dried (sodium sulfate), and concentrated. Some non-polar impurities were removed by passing the residue through silica gel, eluting with 50% ethyl acetate in hexane. The ketone was then transferred to a flask containing anhydrous ammonium trifluoroacetate (4 g) using a minimum amount of ether-methylene chloride. The mixture was placed under vacuum to remove the solvent, and then placed in a preheated oil bath (150° C.). Once all solid had melted and efficient stirring was achieved (approx. 10 min.) the formation of the imidazole was found to be complete. The heating bath was removed and the solids were partitioned between ethyl acetate and water (150/50 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated. The product was purified by filtration through silica gel (imidazole is the least polar component) using ethyl acetate to yield 735 mg of a foam.

Provenance & Evidence