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

HRID 1685376Notes

Reaction equation

HRID 1685376 reaction equation
[CH:1]([N:4]1[C:8](=[O:9])[C:7]([CH3:16])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:6][C:5]1=[O:17])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:21][C:22]([O:24][CH3:25])=[O:23].C([O-])(O)=O.[Na+]>C1COCC1>[CH:1]([N:4]1[C:8](=[O:9])[C:7]([CH3:16])([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:6]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[C:5]1=[O:17])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 516892Sodium BicarbonateHCID 58550608HCID 58550608, compound

Product 1

HCID 86642550Methyl (3-isopropyl-5-methyl-2,4-dioxo-5-phenylimidazolin-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  1. extractionextracted with EtOAc (2×250 mL)
  2. washThe combined organic extracts were washed with brine (100 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

Sources & evidence

ORD record
ord-823ba1dc05ed4f4cb7ba00d55dfa99e7
Source dataset
uspto-grants-2012_04
Patent number
US08148390B2

Reaction notes

Loading…