Methanol → 4-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid

HRID 1676401Notes

Reaction equation

HRID 1676401 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][N:11]=[C:10](C#N)[C:9]2=[O:16])=[CH:4][CH:3]=1.[OH:17]S(O)(=O)=O.[CH3:22][OH:23]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][N:11]=[C:10]([C:22]([OH:17])=[O:23])[C:9]2=[O:16])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 1118Sulfuric AcidHCID 673472474-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carbonitrile

Product 1

HCID 673494894-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid

Procedure

A mixture of 4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carbonitrile (0.42 g, 1.95 mmol) and H2SO4 (4.16 mL, 78.1 mmol) was stirred at room temperature for 17 hours. Then the reaction mixture (amide intermediate) was added to MeOH (50 mL), and then the reaction was heated to 70° C. for 2.5 hours. The reaction mixture (methyl ester compound) was quenched with ice-water and treated with aq. 2N NaOH solution (for hydrolysis) at 0° C. The mixture was acidified with aq. 1N HCl, extracted with EtOAc, dried over MgSO4, and concentrated to afford 0.315 g (69% for 3-step process in one pot reaction) of the desired product which was rinsed with Et2O. 1H-NMR (400 MHz, DMSO-d6) δ 7.90 (d, 1H), 7.60 (m, 2H), 7.52 (d, 1H), 7.42 (t, 2H).

Workup

  1. temperaturethe reaction was heated to 70° C. for 2.5 hours
  2. customThe reaction mixture (methyl ester compound) was quenched with ice-water
  3. additiontreated with aq. 2N NaOH solution (for hydrolysis) at 0° C
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto afford

Sources & evidence

ORD record
ord-e60ee085bea948ec99847ad95433e725
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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