Malonate Ion → 3-[(2-chlorophenyl)methyl]-2-propylthio-N-acetylhistidine

HRID 1757153Notes

Reaction equation

HRID 1757153 reaction equation
[ClH:1].Cl[CH2:3][C:4]1[NH:8][C:7]([S:9][CH2:10][CH2:11][CH3:12])=[N:6][CH:5]=1.[C:13]([NH:16][CH:17]([C:23]([O:25]CC)=[O:24])C(OCC)=O)(=[O:15])[CH3:14].[Na].[H-].[Na+].C(N[CH:35]([C:41](OCC)=O)[C:36](OCC)=O)(=O)C.[C:46]([O-])(=O)[CH2:47][C:48]([O-])=O.[C:53](=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(O)C.O>[Cl:1][C:53]1[CH:48]=[CH:47][CH:46]=[CH:41][C:35]=1[CH2:36][N:8]1[C:4]([CH2:3][C@@H:17]([C:23]([OH:25])=[O:24])[NH:16][C:13](=[O:15])[CH3:14])=[CH:5][N:6]=[C:7]1[S:9][CH2:10][CH2:11][CH3:12]

Participants

10

Reactant 6

HCID 9084Malonate IonHCID 10340Sodium CarbonateHCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 867489125-chloromethyl-2-propylthio-1H-imidazole hydrochlorideHCID 86748914Sodium diethyl acetamidomalonate

Product 1

HCID 540212333-[(2-chlorophenyl)methyl]-2-propylthio-N-acetylhistidine

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

Crude 1-(2-chlorophenyl)methyl)-5-chloromethyl-2-propylthio-1H-imidazole hydrochloride (0.3 g, 0.853 mmole) in dimethyl formamide (2 mL) was added to sodium diethyl acetamidomalonate (prepared by introducing sodium hydride (2.84 mmol) to a solution of diethyl acetamidomalonate (0.415 g, 1.91 mmol) in dimethyl formamide (3 mL)). The mixture was stirred under argon at 25° C. for 18 hours, poured into water and the product was extracted into methylene chloride. The water-washed organic extracts were dried and concentrated in vacuo to a light orange product. This crude product was purified over silica gel with 1:1 hexane/ethyl acetate to afford 0.27 g of the malonate addition product. This product was hydrolyzed in 50% aqueous ethanol (20 mL) and sodium carbonate (0.85 g) in water (20 mL) on the steam bath for 3 hours. The reaction mixture was poured into water and extracted with methylene chloride. The washed, dried, concentrated product (0.23 g) was purified by prep TLC on silica gel with a system of 15% methanol in chloroform containing 0.5% of formic acid to provide 0.13 g of 3-[(2-chlorophenyl)methyl]-2-propylthio-N-acetylhistidine as an amorphous solid; m.p. 182°-184° C.

Workup

  1. customprepared
  2. extractionthe product was extracted into methylene chloride
  3. washThe water-washed organic extracts
  4. customwere dried
  5. concentrationconcentrated in vacuo to a light orange product
  6. customThis crude product was purified over silica gel with 1:1 hexane/ethyl acetate
  7. customto afford
  8. extractionextracted with methylene chloride
  9. customThe washed, dried
  10. customconcentrated product (0.23 g) was purified by prep TLC on silica gel with a system of 15% methanol in chloroform containing 0.5% of formic acid

Sources & evidence

ORD record
ord-df89878ec1ab482faa41bface082df5f
Source dataset
uspto-grants-1995_08
Patent number
US05444081

Reaction notes

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