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

HRID 1985190Notes

Reaction equation

HRID 1985190 reaction equation
C([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)C.[H-].[Na+].[CH3:34][O:35][C:36]1[CH:43]=[CH:42][CH:41]=[CH:40][C:37]=1[CH2:38]Cl.[OH-].[Na+]>CN(C=O)C.C(O)C>[CH3:34][O:35][C:36]1[CH:43]=[CH:42][CH:41]=[CH:40][C:37]=1[CH2:38][N:19]1[CH2:20][CH:16]([CH2:15][CH2:14][O:13][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][C:5]([CH3:30])([O:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:4]([OH:31])=[O:3])=[CH:12][CH:11]=2)[N:17]([CH3:22])[C:18]1=[O:21]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 814952-(Chloromethyl)anisoleHCID 688674462-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester

Product 1

HCID 688690123-(4-{2-[1-(2-Methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acidYield 53%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 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 (0.12 g, 0.281 mmol) in DMF (7 mL) is treated with NaH (60% oil suspension, 0.023 g, 0.575 mmol) and stirred at room temperature under N2 for 20 minutes. The reaction is treated with 2-methoxybenzyl chloride (0.066 g, 0.421 mmol) and then warmed to room temperature and stirred for 3 h. The reaction is quenched with 1 N HCl (10 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 dissolved in ethanol (20 mL) is treated with aqueous 5 N NaOH (1.5 mL) and heated to ref lux 1 h. The reaction mixture is cooled, the solvent removed in vacuo. The resultant residue is acidified with aqueous 1 N HCl (20 mL) and extracted with CH2Cl2. The organic layer is dried (Na2SO4) and the solvent removed in vacuo to afford crude acid that is purified by preparative HPLC to give 0.077 g (53%) of 3-(4-{2-[1-(2-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid. 1H NMR. HRMS (ES+) m/z exact mass calc'd for C30H35N2O6 (M+1) 519.2495. Found m/z 519.2515.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 3 h
  3. customThe reaction is quenched with 1 N HCl (10 mL)
  4. dry with materialThe organic layer is dried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customto afford crude product that
  7. temperatureheated
  8. waitto ref lux 1 h
  9. temperatureThe reaction mixture is cooled
  10. customthe solvent removed in vacuo
  11. extractionextracted with CH2Cl2
  12. dry with materialThe organic layer is dried (Na2SO4)
  13. customthe solvent removed in vacuo
  14. customto afford crude acid that
  15. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-c8757bbb92fe415bbfd503f2a2705b40
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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