Cyanoacetamide → Ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3-pyridinecarboxylate

HRID 2249234Notes

Reaction equation

HRID 2249234 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([CH3:8])=O)[CH3:2].C[O:11][CH:12](OC)[N:13](C)C.[C:18]([CH2:20][C:21](N)=O)#[N:19].[H-].[Na+]>C1COCC1.C(O)(=O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:21]=[C:20]([C:18]#[N:19])[C:12](=[O:11])[NH:13][C:6]=1[CH3:8])=[O:9])[CH3:2]

Participants

7

Reactant 4

HCID 7898CyanoacetamideHCID 8868Ethyl AcetoacetateHCID 24758Sodium hydrideHCID 78373Dimethylformamide dimethyl acetal

Product 1

HCID 3016759Ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3-pyridinecarboxylateYield 45.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethylacetoacetate (6.5 g, 0.050 mole) and dimethylformamide dimethyl acetal (7.14 g, 0.060 mole) were stirred together under argon overnight. The resulting reddish oil was concentrated on the rotary evaporator and the concentrate then dissolved in THF (10 ml) and quickly added to a suspension of cyanoacetamide (4.20 g, 0.050 mole) and sodium hydride in THF (175 ml). The reaction mixture was heated and stirred overnight at 50° C. The reaction mixture was neutralized to pH 6 with acetic acid and concentrated on the rotary evaporator. The residue was triturated with a 50:50 CH2Cl2 -H2O mixture collected and recrystallized (EtOAC) giving 4.7 g of 3-cyano-1,2-dihydro-6-methyl-2-oxo-5-pyridinecarboxylic acid ethyl ester m.pt. 208°-210° C.

Workup

  1. concentrationThe resulting reddish oil was concentrated on the rotary evaporator
  2. concentrationthe concentrate
  3. dissolutionthen dissolved in THF (10 ml)
  4. temperatureThe reaction mixture was heated
  5. concentrationconcentrated on the rotary evaporator
  6. customThe residue was triturated with a 50:50 CH2Cl2 -H2O mixture
  7. customcollected
  8. customrecrystallized (EtOAC)

Sources & evidence

ORD record
ord-62a1c7d7c62b46798ff479ab49066a46
Source dataset
uspto-grants-1991_08
Patent number
US05043449

Reaction notes

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