Sodium hydride → HCID 68867469, compound

HRID 1985204Notes

Reaction equation

HRID 1985204 reaction equation
[H-].[Na+].C([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)C.[CH:34]([C:37]1[CH:44]=[CH:43][C:40]([CH2:41]Cl)=[CH:39][CH:38]=1)([CH3:36])[CH3:35]>CN(C=O)C>[CH:34]([C:37]1[CH:44]=[CH:43][C:40]([CH2:41][N:21]2[CH2:22][CH:18]([CH2:17][CH2:16][O:15][C:12]3[CH:11]=[CH:10][C:9]([CH2:8][C:7]([CH3:32])([O:25][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:6]([OH:33])=[O:5])=[CH:14][CH:13]=3)[N:19]([CH3:24])[C:20]2=[O:23])=[CH:39][CH:38]=1)([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 749164-Isopropylbenzyl chlorideHCID 688674462-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester

Product 1

HCID 68867469HCID 68867469, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cooled (0° C.) suspension of NaH (24 mg, 0.60 mmol, 60% w/w in mineral oil) in DMF (1 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 (128 mg, 0.30 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 45 minutes. After the solution is cooled again to 0° C., 4-isopropylbenzyl chloride (126 mg, 0.75 mmol) is added in a single portion, the cooling bath removed, and the mixture stirred for 50 minutes. 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 dissolved in ethanol (4 ml), treated with 5N NaOH (1.5 ml), and stirred for 24 hours at ambient temperature. The mixture is poured into 1N HCl, then extracted with ethyl acetate (2×20 ml). The combined ethyl acetate extracts were washed with water, brine, dried (Na2SO4), and concentrated to an oil which is purified by MS/LC to provide a foam (110 mg, 69%).

Workup

  1. temperatureTo a cooled
  2. customthe reaction mixture is removed from the cooling bath
  3. temperatureAfter the solution is cooled again to 0° C.
  4. customthe cooling bath removed
  5. stirringthe mixture stirred for 50 minutes
  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. dissolutionThe crude product is dissolved in ethanol (4 ml)
  12. additiontreated with 5N NaOH (1.5 ml)
  13. stirringstirred for 24 hours at ambient temperature
  14. additionThe mixture is poured into 1N HCl
  15. extractionextracted with ethyl acetate (2×20 ml)
  16. washThe combined ethyl acetate extracts were washed with water, brine
  17. dry with materialdried (Na2SO4)
  18. concentrationconcentrated to an oil which
  19. customis purified by MS/LC

Sources & evidence

ORD record
ord-7418a1c6e3f1417483ed30a515a59657
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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