Phosgene → Racemic-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride

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Reaction Conditions

Reaction Steps

To a solution of 2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-1H-imidazole (19.7 g, 42.144 mmol) and triethylamine (17.6 mL, 126.432 mmol) in methylene chloride (200 mL) cooled to 0° C. was added phosgene (44.6 mL, 84.288 mmol, 20% solution in toluene, Fluka). The reaction mixture was stirred at 0° C. for 30 min then concentrated to dryness. The orange residue was taken in methylene chloride (100 mL), and the solution was filtered through a plug of silica gel (50 g). It was washed with methylene chloride (˜600 mL). The filtrate was concentrated, and the residue was purified by flash chromatography (silica gel, eluting with 10% ethyl acetate in hexane) to give racemic-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride as white solids (12.650 g). The enantiomers of 2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride were separated by chiral chromatography using a Waters Delta Prep 4000 and Modcol spring column (50 mm×70 cm) packed with R,R-Whelk-O1 spherical Kromasil silica gel (purchased from Regis Technologies). Eluent: 30% methylene chloride in hexane. Flowrate: 85 mL/min. Loading scale: 2.4-3.0 g. The first peak coming off the column is the desired (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride.

Provenance & Evidence