Sodium Hydroxide → 6-(4-methoxy-2-methylphenyl)-5-methylpyrazin-2(1H)-one

HRID 69324Notes

Reaction equation

HRID 69324 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[C:10](=O)[CH3:11])=[C:5]([CH3:14])[CH:4]=1.C(O)(=O)C.[NH2:19][CH2:20][C:21]([NH2:23])=[O:22].[OH-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:23][C:21](=[O:22])[CH:20]=[N:19][C:10]=2[CH3:11])=[C:5]([CH3:14])[CH:4]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 203984852-Aminoacetamide acetateHCID 867178221-(4-Methoxy-2-methylphenyl)propane-1,2-dione

Product 1

HCID 867178236-(4-methoxy-2-methylphenyl)-5-methylpyrazin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-10 °C

Procedure

C9 (4.0 g, 21 mmol) and glycinamide acetate (2.79 g, 20.8 mmol) were dissolved in methanol (40 mL) and cooled to −10° C. Aqueous sodium hydroxide solution (12 N, 3.5 mL, 42 mmol) was added, and the resulting mixture was slowly warmed to room temperature. After stirring for 3 days, the reaction mixture was concentrated in vacuo. The residue was diluted with water, and 1 N aqueous hydrochloric acid was added until the pH was approximately 7. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was slurried with 3:1 ethyl acetate/heptane, stirred for 5 minutes, filtered, and concentrated in vacuo. Silica gel chromatography (Eluent: ethyl acetate) provided the product as a tan solid that contained 15% of an undesired regioisomer; this material was used without further purification. Yield: 2.0 g. LCMS m/z 231.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.14 (d, J=8.2 Hz, 1H), 6.82-6.87 (m, 2H), 3.86 (s, 3H), 2.20 (s, 3H), 2.11 (s, 3H).

Workup

  1. temperaturethe resulting mixture was slowly warmed to room temperature
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additionThe residue was diluted with water, and 1 N aqueous hydrochloric acid
  4. additionwas added until the pH was approximately 7
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. washthe combined organic extracts were washed with saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. stirringstirred for 5 minutes
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96ed6d7564524d30a60764fc9716f6e7
Source dataset
uspto-grants-2014_09
Patent number
US08822494B2

Reaction notes

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