Water → Ethyl 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrate

HRID 1994290Notes

Reaction equation

HRID 1994290 reaction equation
[CH2:1]([O:8][C:9]1[CH:21]=[CH:20][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][NH:16][C:15]2=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH:25]([CH:31]([CH3:33])[CH3:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27].O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:21]=[CH:20][C:12]([CH2:13][N:14]2[CH2:18][CH2:17][N:16]([CH:25]([CH:31]([CH3:33])[CH3:32])[C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:15]2=[O:19])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 79068Ethyl 2-bromoisovalerateHCID 215651681-{[4-(Benzyloxy)phenyl]methyl}imidazolidin-2-one

Product 1

HCID 68538627Ethyl 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrateYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

1-(4-Benzyloxybenzyl)imidazolidin-2-one (1.0 g; 3.54 mmol) was dissolved in dimethylformamide (DMF, 10 ml). NaH (60% in mineral oil; 0.085 g; 3.54 mol) was added, and the mixture was heated at 40° C. for 1 h. Then ethyl 2-bromoisovalerate (0.74 g; 3.54 mmol) were added, and heating was continued at 60° C. for 4 h. The reaction was stopped by slow addition of water (1 ml). The solvent was removed under reduced pressure, and the residue was partitioned between water (50 ml) and EtOAc (50 ml). Dilute HCl was added until the pH of the aqueous phase was about 4. The phases were then separated, and the aqueous phase was extracted with EtOAc (2×; 30 ml). The combined organic phases were dried over MgSO4. The solvent was removed under reduced pressure. Purification of the residue by column chromatography on silica gel (SiO2) resulted in ethyl 2-(3-(4-benzyloxybenzyl)-2-oxoimidazolidin-1-yl)-3-methylbutyrate (0.38 g; 0.92 mmol). MS: 411.15 (M+H); Rt: 1.87 min (method: gradient 0 min 90% H2O (0.05% TFA) 1.9 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 10% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)

Workup

  1. temperatureheating
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between water (50 ml) and EtOAc (50 ml)
  4. additionDilute HCl was added until the pH of the aqueous phase
  5. customThe phases were then separated
  6. extractionthe aqueous phase was extracted with EtOAc (2×; 30 ml)
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. customThe solvent was removed under reduced pressure
  9. customPurification of the residue by column chromatography on silica gel (SiO2)

Sources & evidence

ORD record
ord-55316aad2470419fbc11327e42149cb5
Source dataset
uspto-grants-2010_01
Patent number
US07652143B2

Reaction notes

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