Sodium hydride → Methyl 4-(3,4-difluorobenzyl)-3-oxo-3,4-dihydropyrazine-2-carboxylate

HRID 1038977Notes

Reaction equation

HRID 1038977 reaction equation
[OH:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[F:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:18]Br.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.CN(C=O)C>[F:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[F:23])[CH2:18][N:3]1[CH:4]=[CH:5][N:6]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:2]1=[O:1]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 178499100HCID 178499100, compound

Product 1

HCID 58443085Methyl 4-(3,4-difluorobenzyl)-3-oxo-3,4-dihydropyrazine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 2-hydroxy-3-pyrazinecarboxylate (103 mg, 0.67 mmol) (obtained from Fulcrum Scientific Ltd.) was placed in a 25-mL RBF and placed under a nitrogen atmosphere. DMF (3 mL) was added, followed by NaH (33 mg, 0.83 mmol) and the reaction was allowed to stir for twenty minutes at room temperature. 3,4-Difluorobenzyl bromide (0.094 mL, 0.735 mmol) was added, and the reaction was allowed to stir at room temperature overnight, and the reaction was found to be complete by LC-MS. The reaction was added to a separatory funnel containing ethyl acetate (125 mL) and dilute aqueous NaHCO3 (75 mL); the phases were separated and the organic layer was washed with brine and dried over anhydrous Na2SO4, then concentrated in vacuo. The crude product was purified by silica gel chromatography using 10-100% EtOAc in n-heptane to afford methyl 4-(3,4-difluorobenzyl)-3-oxo-3,4-dihydropyrazine-2-carboxylate as a yellow solid. 1H NMR (500 MHz, C2D6SO) δ 8.08 (d, 1H), 7.49 (t, 1H), 7.44 (d, 1H), 7.42 (t, 1H), 7.23 (m, 1H), 5.09 (s, 2H), 3.80 (s, 3H). LRMS (ESI) calc'd for (C13H11F2N2O3) [M+H]+, 281.1; found 281.1.

Workup

  1. stirringto stir at room temperature overnight
  2. additionThe reaction was added to a separatory funnel
  3. customthe phases were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-75308c248bbb49a9a6e83bdaca9d7b3b
Source dataset
uspto-grants-2013_10
Patent number
US08552019B2

Reaction notes

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