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

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).

1. extractionextracted with EtOAc (3×250 mL)
2. washThe combined organic extracts were washed with water (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified by silica gel chromatography
7. washeluting with a gradient of hexane

ORD record

ord-1dd04a8e5bd0421f86fbf350a246928e

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148390B2