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

HRID 865224Notes

Reaction equation

HRID 865224 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][N:10]1[C:14]([CH2:15]Cl)=[CH:13][N:12]=[C:11]1[S:17][CH2:18][CH2:19][CH3:20].[C:21]([NH:24][CH:25](C(OCC)=O)[C:26]([O:28]CC)=[O:27])(=[O:23])[CH3:22].[Na].[H-].[Na+].C(NC(C(OCC)=O)C(OCC)=O)(=O)C.C([O-])(=O)CC([O-])=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(O)C.O>[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][N:10]1[C:14]([CH2:15][C@@H:25]([C:26]([OH:28])=[O:27])[NH:24][C:21](=[O:23])[CH3:22])=[CH:13][N:12]=[C:11]1[S:17][CH2:18][CH2:19][CH3:20]

Participants

10

Reactant 6

HCID 9084Malonate IonHCID 10340Sodium CarbonateHCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 19351525HCID 19351525, compoundHCID 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 (3mL)). 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-6228152819a14ed9a66e9b80d1e6b2f9
Source dataset
uspto-grants-1996_10
Patent number
US05565480

Reaction notes

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