Acetamidomalonic acid diethyl ester → HCID 21834431, compound

HRID 1740964Notes

Reaction equation

HRID 1740964 reaction equation
[H-].[Na+].[C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4].CS(O[CH2:23][CH2:24][C:25]1[N:30]=[C:29]([N:31]2C(C)=CC=C2C)[CH:28]=[C:27]([CH3:38])[CH:26]=1)(=O)=O>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:3]([NH:6][C:7]([CH2:23][CH2:24][C:25]1[CH:26]=[C:27]([CH3:38])[CH:28]=[C:29]([NH2:31])[N:30]=1)([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4]

Participants

6

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 21834439HCID 21834439, compound

Product 1

HCID 21834431HCID 21834431, compoundYield 106.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Sodium hydride (52 mg of 60% oil dispersion, 1.30 mmol) was added to a solution of 310 mg (1.43 mmol) of diethyl acetamidomalonate in 2.0 mL of N,N-dimethylformamide. After 30 min, 72 mg (0.20 mmol) of tetrabutylammonium iodide was added followed by 200 mg (0.65 mmol) of 6 -(2-methanesulfonyloxyethyl)-4-methyl-2-(2,5-dimethylpyrrol-1-yl)pyridine in 1.0 mL of N,N-dimethylformamide. The reaction was stirred at room temperature for 30 min, at 60° C. for 20 h, and at room temperature for 3 d. The reaction was diluted with 30. mL of ethyl acetate and washed with 15 mL each of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The aqueous layers were extracted in succession with 30 mL of ethyl acetate. The combined organic layers were dried (sodium sulfate), decanted, and evaporated. The crude product was purified by flash column chromatography on 15 g of silica gel, eluting with 300 mL of 10% ethyl acetate in dichloromethane to give 243 mg (87% yield) of diethyl 2-acetamido-2-(2-(6-amino-4-methylpyrid-2-yl)ethyl)malonate as a tan solid.

Workup

  1. waitat room temperature for 3 d
  2. additionThe reaction was diluted with 30
  3. washmL of ethyl acetate and washed with 15 mL each of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  4. extractionThe aqueous layers were extracted in succession with 30 mL of ethyl acetate
  5. dry with materialThe combined organic layers were dried (sodium sulfate)
  6. customdecanted
  7. customevaporated
  8. customThe crude product was purified by flash column chromatography on 15 g of silica gel
  9. washeluting with 300 mL of 10% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-cb7e3046117e472b9a8388c12706a5e1
Source dataset
uspto-grants-1999_10
Patent number
US05972975

Reaction notes

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