Diisopropylethylamine → HCID 178468168, compound

Participants

Reaction Conditions

Reaction Steps

Diisopropylethylamine (0.24 mL, 1.37 mmol) was added to a solution of 2-({1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}amino)-4-methylphenol (D29, 215 mg, 0.648 mmol) in dichloromethane (8 mL) at rt under argon. The reaction was cooled to 0° C. and the triphosgene (79 mg, 0.267 mmol) was added. The mixture was stirred for 30 min at 0° C., followed by a further 15 min at rt. The reaction was quenched with saturated aqueous NaHCO3 (10 mL) and partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane (2×) and the combined organics were dried (Na2SO4) and concentrated by rotary evaporation to give a white solid. The residue was purified via chromatography (silica, dichloromethane to 0.5% ammonia/9.5% methanol/90% dichloromethane) to give the free base of the title compound as a white solid. The free base was dissolved in diethyl ether (1.5 mL) at 25° C. HCl (0.207 mL, 0.207 mmol, 1 M in diethyl ether) was then added and the reaction was stirred for 15 min. The solvent was removed by rotary evaporation to give 3-{1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}-5-methyl-1,3-benzoxazol-2(3H)-one hydrochloride (E10, 39.3 mg, 14% yield) as a white solid.

Provenance & Evidence