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

HRID 1985189Notes

Reaction equation

HRID 1985189 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+].F[C:35](F)(F)[C:36]1[CH:43]=[CH:42][CH:41]=[CH:40][C:37]=1CBr.[OH-].[Na+].CN([CH:51]=[O:52])C>C(O)C>[CH3:51][O:52][C:40]1[CH:37]=[C:36]([CH:43]=[CH:42][CH:41]=1)[CH2:35][N:19]1[CH2:20][CH:16]([CH2:15][CH2:14][O:13][C:10]2[CH:11]=[CH:12][C:7]([CH2:6][C:5]([CH3:30])([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:4]([OH:3])=[O:31])=[CH:8][CH:9]=2)[N:17]([CH3:22])[C:18]1=[O:21]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 1230571-(Bromomethyl)-2-(trifluoromethyl)benzeneHCID 688674462-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester

Product 1

HCID 688668373-(4-{2-[1-(3-Methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acidYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester (0.109 g, 0.255 mmol) in DMF (7 mL) is treated with NaH (60% oil suspension, 0.021 g, 0.525 mmol) and stirred at room temperature under N2 for 20 minutes. The reaction is treated with 2-trifluoromethyl benzyl bromide (0.092 g, 0.385 mmol) and then warmed to room temperature and stirred for 3 hours. The reaction is quenched with acid and worked up extractively with Et2O and water. The organic layer is dried and the solvent removed to afford crude product that is dissolved in ethanol (20 mL) is treated with aqueous 5 N NaOH (1.5 mL) and heated to reflux 1 hour. The reaction mixture is cooled, the solvent removed. The resultant residue is acidified with aqueous 1 N HCl (20 mL) and extracted with CH2Cl2. The organic layer is dried and the solvent removed in vacuo to afford crude acid that is purified by preparative HPLC to give 0.096 g (68%) of 2-methyl-3-(4-{2-[3-methyl-2-oxo-1-(2-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-2-phenoxy-propionic acid 1H NMR. HRMS (ES+) m/z exact mass calc'd for C30H32N2O5F3 (M+1) 557.2263. Found m/z 557.2274.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 3 hours
  3. customThe reaction is quenched with acid
  4. customThe organic layer is dried
  5. customthe solvent removed
  6. customto afford crude product that
  7. temperatureheated
  8. temperatureto reflux 1 hour
  9. temperatureThe reaction mixture is cooled
  10. customthe solvent removed
  11. extractionextracted with CH2Cl2
  12. customThe organic layer is dried
  13. customthe solvent removed in vacuo
  14. customto afford crude acid that
  15. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-046279c576d6409d9a09809e40f8044b
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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