Sodium hydride → 3-(4-{2-[1-(4-Benzoyl-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl ester

HRID 1985203Notes

Reaction equation

HRID 1985203 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:33])[C:7]([CH3:32])([O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH:18]2[CH2:22][NH:21][C:20](=[O:23])[N:19]2[CH3:24])=[CH:11][CH:10]=1)[CH3:4].Br[CH2:35][C:36]1[CH:49]=[CH:48][C:39]([C:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:41])=[CH:38][CH:37]=1>CN(C=O)C>[CH2:3]([O:5][C:6](=[O:33])[C:7]([CH3:32])([O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][CH:18]2[CH2:22][N:21]([CH2:35][C:36]3[CH:37]=[CH:38][C:39]([C:40](=[O:41])[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[CH:48][CH:49]=3)[C:20](=[O:23])[N:19]2[CH3:24])=[CH:13][CH:14]=1)[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1229514-(Bromomethyl)benzophenoneHCID 688674462-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester

Product 1

HCID 688674533-(4-{2-[1-(4-Benzoyl-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl esterYield 10.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cooled (0° C.) suspension of NaH (45 mg, 1.1 mmol, 60% w/w in mineral oil) in DMF (0.5 ml) is added a solution of 2-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester (320 mg, 0.75 mmol) in DMF (1.5 ml). After 5 minutes, the reaction mixture is removed from the cooling bath and stirred while warming to ambient temperature over 30 minutes. The solution is cooled again to 0° C., and 4-(bromomethyl)benzophenone (188 mg, 0.68 mmol) is added in a single portion, the cooling bath removed, and the mixture stirred for one hour. The reaction mixture is quenched with 1N HCl and extracted with ethyl acetate (2×). The organic extracts were washed with water, brine, dried (Na2SO4), and concentrated to an oil. The crude product is purified by flash chromatography on a Biotage silica cartridge (gradient elution, 2:1 hexanes:ethyl acetate to 1:2 hexanes:ethyl acetate) to provide an oil (46 mg, 10%).

Workup

  1. temperatureTo a cooled
  2. customthe reaction mixture is removed from the cooling bath
  3. temperatureThe solution is cooled again to 0° C.
  4. customthe cooling bath removed
  5. stirringthe mixture stirred for one hour
  6. customThe reaction mixture is quenched with 1N HCl
  7. extractionextracted with ethyl acetate (2×)
  8. washThe organic extracts were washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to an oil
  11. customThe crude product is purified by flash chromatography on a Biotage silica cartridge (gradient elution, 2:1 hexanes:ethyl acetate to 1:2 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-563754990b4e4571a82ce475b718f3b1
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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