Sodium hydride → Methyl (3-isopropyl-5-methyl-2,4-dioxo-5-phenylimidazolin-1-yl)acetate

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Reaction Steps

To a stirred solution of (t)-3-isopropyl-5-methyl-5-phenyl imidazoline-2,4-dione from Step A (1.0 g, 4.3 mmol) in THF (50 mL) at 0° C. was added NaH (220 mg of a 60% dispersion in oil, 5.6 mmol). After 5 min, methyl bromoacetate (0.69 g, 4.52 mmol) was added and the mixture was stirred for 1 h. The reaction mixture was warmed to ambient temperature and then poured into saturated aqueous NaHCO3 (200 mL) and extracted with EtOAc (2×250 mL). The combined organic extracts were washed with brine (100 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—90:10 to 50:50, to give racemic title compound. The enantiomers were resolved by HPLC, utilizing a ChiralPak OD column and eluting with hexane:EtOH 60:40. The first major peak to elute was methyl (3-isopropyl-5-methyl-2,4-dioxo-5-phenylimidazolin-1-yl)acetate, isomer A, and the second major peak to elute was methyl (3-isopropyl-5-methyl-2,4-dioxo-5-phenylimidazolin-1-yl)acetate, isomer B, the title compound. MS: m/z=305 (M+1).

Provenance & Evidence