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

HRID 1985187Notes

Reaction equation

HRID 1985187 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[C:5]([CH3:30])([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][NH:19][C:18](=[O:21])[N:17]2[CH3:22])=[CH:9][CH:8]=1)[CH3:2].[H-].[Na+].[CH3:34][O:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=1)[CH2:39]Br>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:3][C:4](=[O:31])[C:5]([CH3:30])([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:39][C:38]3[CH:41]=[CH:42][CH:43]=[C:36]([O:35][CH3:34])[CH:37]=3)[C:18](=[O:21])[N:17]2[CH3:22])=[CH:11][CH:12]=1)[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 40672073-Methoxybenzyl bromideHCID 688674462-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester

Product 1

HCID 688696793-(4-{2-[1-(3-Methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl esterYield 55%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester (0.40 g, 0.94 mmol) in DMF (10 mL) is treated with NaH (60% oil suspension, 0.094 g, 2.35 mmol) and stirred at room temperature under N2 for 30 minutes. The reaction is cooled to 0° C. and treated with tetrabutylammonium iodide (0.040 g, 0.11 mmol) and 3-methoxybenzyl bromide (0.29 g, 1.43 mmol) and then warmed to room temperature and stirred for 1.5 h. The reaction is quenched with 1 N HCl (15 mL) and worked up extractively with Et2O and water. The organic layer is dried (MgSO4) and the solvent removed in vacuo to afford crude product that is purified by flash chromatography using 2:1 hexanes:acetone to afford 0.28 g (55%) 3-(4-{2-[1-(3-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl ester. 1H NMR. Rf=0.41 (1:1 acetone:hexanes). MS (ES+) Calc'd for C32H39N2O6 (M+1) 547. Found m/z 547 (100%).

Workup

  1. temperatureThe reaction is cooled to 0° C.
  2. temperaturewarmed to room temperature
  3. stirringstirred for 1.5 h
  4. customThe reaction is quenched with 1 N HCl (15 mL)
  5. dry with materialThe organic layer is dried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customto afford crude product that
  8. customis purified by flash chromatography

Sources & evidence

ORD record
ord-53754c47b0684bd990b69d2ec6c82412
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

Loading…