Acetic Acid → 3-Methoxy-5-phenyl-pyrazine-2-carboxylic acid methyl ester

HRID 1609832Notes

Reaction equation

HRID 1609832 reaction equation
[C:1]1([CH3:11])C=CC(S(O)(=O)=O)=C[CH:2]=1.[NH2:12][CH:13]([C:16]#[N:17])[C:14]#N.[CH3:18][O-:19].[Na+].[C:21]([OH:24])(=O)C.C(=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28]C=1.Cl.C[OH:35]>>[CH3:18][O:19][C:11]([C:1]1[C:2]([O:24][CH3:21])=[N:12][C:13]([C:14]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:26]=2)=[CH:16][N:17]=1)=[O:35]

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 887MethanolHCID 563049Aminomalononitrile p-toluenesulphonateHCID 10942334Sodium Methoxide

Product 1

HCID 235896503-Methoxy-5-phenyl-pyrazine-2-carboxylic acid methyl ester

Conditions

Temperature
0 °C

Procedure

To a solution of 2-amino-malononitrile 4-toluenesufonate (5.0 g, 19.3 mmol) in methanol (60 mL) at room temperature under N2 is added NaOMe (25% w/w in MeOH, 5.2 mL, 22.7 mmol). After 2 hours, acetic acid (0.204 g, 3.4 mmol) is added. The mixture is cooled to 0° C. and to the mixture is added benzaldehyde (3 g, 19.9 mmol). The mixture is stirred at this temperature for an additional 2 hours and then gradually warmed to room temperature overnight. To the mixture is added concentrated HCl (9.2 g, 80 mmol) and the mixture is stirred at room temperature over the weekend. Solvent is removed in vacuo. To the crude mixture is added saturated NH4Cl (50 mL) and DCM (100 mL). The organic layer is separated and the aqueous layer is extracted (2×50 mL) with DCM. The combined organic layers are dried and solvent removed. Column chromatography separation (silica gel, DCM) gives 1.0 g of 3-methoxy-5-phenyl-pyrazine-2-carboxylic acid methyl ester as a yellow solid.

Workup

  1. temperaturegradually warmed to room temperature overnight
  2. stirringthe mixture is stirred at room temperature over the weekend
  3. customSolvent is removed in vacuo
  4. additionTo the crude mixture is added saturated NH4Cl (50 mL) and DCM (100 mL)
  5. customThe organic layer is separated
  6. extractionthe aqueous layer is extracted (2×50 mL) with DCM
  7. customThe combined organic layers are dried
  8. customsolvent removed
  9. customColumn chromatography separation (silica gel, DCM)

Sources & evidence

ORD record
ord-c2558659e8234cbd807b2dcd11718a08
Source dataset
uspto-grants-2006_01
Patent number
US06982268B2

Reaction notes

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