Butyl iodide → 2-Butoxy-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester

HRID 1985150Notes

Reaction equation

HRID 1985150 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[C:5]([OH:33])([CH3:32])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:18](=[O:30])[N:17]2[CH3:31])=[CH:9][CH:8]=1)[CH3:2].[H-].[Na+].I[CH2:38][CH2:39][CH2:40][CH3:41].C1OCCOCCOCCOCCOCCOC1>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:34])[C:5]([O:33][CH2:38][CH2:39][CH2:40][CH3:41])([CH3:32])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[C:18](=[O:30])[N:17]2[CH3:31])=[CH:11][CH:12]=1)[CH3:2]

Participants

7

Reactant 4

HCID 10962Butyl iodideHCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 68867294HCID 68867294, compound

Product 1

HCID 688706692-Butoxy-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A slurry of 2-hydroxy-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester (7.35 g, 15.62 mmol) and sodium hydride (2.5 g, 62.5 mmol, 60% dispersion on mineral oil) in DMF (50 mL) i stirred for 45 minutes, then cooled to 0° C. Iodobutane (36 mL, 312 mmol, d=1.617) and 18-crown-6 16.5 g, 62.5 mmol) are added, then the reaction mixture is stirred 18 h at ambient temperature and diluted with ethyl acetate. The organic layer is washed, then dried concentrated in vacuo, and diluted with ethanol (400 mL) and 5N NaOH (40 mL). The reaction mixture is refluxed for 1 h, cooled to ambient temperature, and concentrated in vacuo. The residue is washed, dried, concentrated, and re-dissolved in ethanol (300 mL). Concentrated H2SO4 (30 mL) is added to the reaction solution, then the mixture is refluxed 1 h, cooled to ambient temperature, concentrated, and diluted with ethyl acetate. The organic layer is washed, dried, and concentrated to provide the title compound (5.3 g, 65%). 1H NMR (400 MHz, CDCl3): δ 7.17 (d, 2H, J=8.8 Hz), 7.09 (d, 2H, J=8.8 Hz), 6.84 (d, 2H, J=8.8 Hz), 6.70 (d, 2H, J=8.8 Hz), 4.32, 4.28 (ABq, 2H, J=14.7 Hz), 4.17-4.11 (m, 2H), 3.93 (t, 2H, J=5.9 Hz), 3.78 (s, 3H), 3.61-3.53 (m, 3H), 3.40-3.31 (m, 3H), 2.97-2.89 (m, 3H), 2.97-2.89 (m, 3H), 2.81 (s, 3H), 2.25-2.15 (m, 1H), 1.89-1.81 (m, 1H), 1.59-1.49 (m, 2H), 1.42-1.33 (m, 2H), 1.29 (s, 3H), 1.24 (t, 3H, J=7.2 Hz), 0.91 (t, 3H, J=7.2 Hz). Rf=0.43 in 50% acetone in hexanes.

Workup

  1. washThe organic layer is washed
  2. customdried
  3. concentrationconcentrated in vacuo
  4. additiondiluted with ethanol (400 mL) and 5N NaOH (40 mL)
  5. temperatureThe reaction mixture is refluxed for 1 h
  6. temperaturecooled to ambient temperature
  7. concentrationconcentrated in vacuo
  8. washThe residue is washed
  9. customdried
  10. concentrationconcentrated
  11. dissolutionre-dissolved in ethanol (300 mL)
  12. additionConcentrated H2SO4 (30 mL) is added to the reaction solution
  13. temperaturethe mixture is refluxed 1 h
  14. temperaturecooled to ambient temperature
  15. concentrationconcentrated
  16. additiondiluted with ethyl acetate
  17. washThe organic layer is washed
  18. customdried
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-7cd6c63824e74da6bd50d5785c62618e
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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