Ethyl bromoacetate → HCID 57743029, compound

HRID 1896365Notes

Reaction equation

HRID 1896365 reaction equation
[CH2:1]([O:3][C:4](=[O:7])[CH2:5]Br)[CH3:2].[CH2:8]([CH:11]1[CH2:15][N:14]([CH2:16][C:17]2[N:18]=[CH:19][N:20](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:21]=2)[C:13](=[O:41])[CH2:12]1)[CH2:9][CH3:10]>C(#N)C>[O:41]=[C:13]1[CH2:12][CH:11]([CH2:8][CH2:9][CH3:10])[CH2:15][N:14]1[CH2:16][C:17]1[N:18]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:7])[CH:19]=[N:20][CH:21]=1

Participants

4

Reactant 2

HCID 7748Ethyl bromoacetate2×HCID 53629158HCID 53629158, compound

Product 1

HCID 57743029HCID 57743029, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

In a 50 ml, three-necked flask fitted with a magnetic stirrer under inert atmosphere, ethylbromoacetate (560 μl, 4.95 mmol) is added to a solution of 4-propyl-1-[(1-trityl-1H-imidazol-4-yl)methyl]pyrrolidin-2-one x45 (1.5 g, 3.3 mmol) in 10 ml of acetonitrile. The mixture is stirred at 40° C. for 3 h, 1.65 mmol of ethylbromoacetate is added and stirring is pursued for 48 h at room temperature. The mixture is concentrated in vacuo, 20 ml of a 1/1 mixture of acetic acid and water is added and the mixture is stirred at room temperature overnight. The mixture is filtered, the solvent is evaporated and the residue is dissolved in 25 ml of diluted HCl (pH 1). The aqueous phase is washed with CH2Cl2, basified to pH 10 by addition of solid Na2CO3 and extracted three times with CH2Cl2. The combined organic phases are dried over MgSO4, filtered and concentrated to dryness. The crude product is purified by tin layer chromatography on preparative plates (CH2Cl2/EtOH: 90/10 (v/v)) to give 275 mg of ethyl {5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazol-1-yl}acetate (30%). Ethyl {5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazol-1-yl}acetate hydrochloride x49 is obtained by treatment with a solution of HCl in Et2O and recrystallization from CH3CN/AcOEt.

Workup

  1. stirringstirring
  2. waitis pursued for 48 h at room temperature
  3. concentrationThe mixture is concentrated in vacuo, 20 ml of a 1/1 mixture of acetic acid and water
  4. additionis added
  5. stirringthe mixture is stirred at room temperature overnight
  6. filtrationThe mixture is filtered
  7. customthe solvent is evaporated
  8. dissolutionthe residue is dissolved in 25 ml of diluted HCl (pH 1)
  9. washThe aqueous phase is washed with CH2Cl2
  10. additionbasified to pH 10 by addition of solid Na2CO3
  11. extractionextracted three times with CH2Cl2
  12. dry with materialThe combined organic phases are dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated to dryness
  15. customThe crude product is purified by tin layer chromatography on preparative plates (CH2Cl2/EtOH: 90/10 (v/v))

Sources & evidence

ORD record
ord-8813edca480c42f7b22c442f28065144
Source dataset
uspto-grants-2013_08
Patent number
US08518943B2

Reaction notes

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