Acetonitrile → Ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate

Participants

Reaction Steps

To a stirred solution of (±)-ethyl[5-(3,5-difluorophenyl)-3-(4-methoxybenzyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate from Step C (11.4 g, 26.3 mmol) in CH3CN (150 mL) was added drop wise a solution of ammonium cerium (IV) nitrate (43.2 g, 78.8 mmol) in water (100 mL) and the resulting mixture was stirred at ambient temperature for 3 h. The reaction was diluted with water (300 mL) and extracted with EtOAc (3×250 mL). The combined organic extracts were washed with water (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 50:50, to give the racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak AD column and eluting with hexane:EtOH:DEA 40:60:1. The first major peak to elute was ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate, isomer A, the title compound, and the second major peak to elute was ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate, isomer B. MS: m/z=313 (M+1).

Provenance & Evidence