Triethylamine → 2-[4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-1H-imidazol-1-YL]carbonyl]-1-piperazinyl]-1-(4-morpholinyl)ethanone

Participants

Reaction Steps

To a solution of (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (7.967 g, 15.03 mmol, example 11) in methylene chloride (60 mL) cooled to 0° C. were added triethylamine (4.19 mL) and 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (3.366 g, 15.78 mmol, Oakwood Products), respectively. The ice bath was removed, and the reaction mixture was stirred at room temperature for 30 min. The reaction was monitored by thin layer chromatography (silica gel, 20% ethyl acetate in hexane). The reaction mixture was concentrated to dryness, and the crude residue was purified by flash column chromatography (silica gel, eluting with 0.1% triethylamine in ethyl acetate) to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone as white foam. The white foam was taken in 100 ml of ethyl acetate then filtered. Hydrogen chloride (18.04 mL, 1 M solution in diethyl ether) was added dropwise to the filtrate. The white solids formed were filtered off and dried in vacuo to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone hydrochloride (9.3 g). HR-MS (ES, m/z) calculated for C38H46N5O4Cl2 [(M+H)+] 706.2922, observed 706.2917.

Provenance & Evidence