Diethyl Malonate → diethyl [1-{(2-chlorophenyl)methyl}-2-propylthio-1H-imidazol-5-yl]methylmalonate

HRID 1757172Notes

Reaction equation

HRID 1757172 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl.Cl[CH2:16][C:17]1[N:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[C:20]([S:30][CH2:31][CH2:32][CH3:33])=[N:19][CH:18]=1>CN(C)C=O>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][N:21]1[C:17]([CH2:16][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[CH:18][N:19]=[C:20]1[S:30][CH2:31][CH2:32][CH3:33]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 19351525HCID 19351525, compound

Product 1

HCID 86748910diethyl [1-{(2-chlorophenyl)methyl}-2-propylthio-1H-imidazol-5-yl]methylmalonateYield 49.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To dry dimethylformamide (10 mL) under argon was added sodium hydride (0.14 g, 5.83 mmol) followed by diethyl malonate (0.92 g, 5.75 mmol) in dimethylformamide (2 mL) at 0° C. The mixture was stirred at ambient temperature for one hour. A solution of 5-chloromethyl-1-(2-chlorophenyl)methyl-2-propylthio-1H-imidazole hydrochloride (1.0 g, 2.84 mmol) in dimethylformamide (4 mL) was added over 5 minutes. The reaction mixture was stirred at 25° C. for 18 hours, then partitioned between water and methylene chloride. The organic layer was washed with water, dried, and concentrated. The crude product was flash chromatographed over silica gel with 1:1 hexane/ethyl acetate to give 0.62 g (49.7%) of diethyl [1-{(2-chlorophenyl)methyl}-2-propylthio-1H-imidazol-5-yl]methylmalonate as a pale yellow syrup.

Workup

  1. stirringThe reaction mixture was stirred at 25° C. for 18 hours
  2. custompartitioned between water and methylene chloride
  3. washThe organic layer was washed with water
  4. customdried
  5. concentrationconcentrated
  6. customchromatographed over silica gel with 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-750bf2a922134b78a1a0e84da6c1faca
Source dataset
uspto-grants-1995_08
Patent number
US05444080

Reaction notes

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