Diethyl Ether → 6,7-Dimethoxy-2-methylquinoxaline

HRID 1859507Notes

Reaction equation

HRID 1859507 reaction equation
Cl[C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][C:6]([O:14][CH3:15])=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.C[Mg+].[Br-].[CH3:19]COCC>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:19][C:2]1[CH:11]=[N:10][C:9]2[C:4](=[CH:5][C:6]([O:14][CH3:15])=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 225731372-Chloro-6,7-dimethoxyquinoxalineHCID 178418689HCID 178418689, compound

Product 1

HCID 1325416,7-Dimethoxy-2-methylquinoxaline

Reagents, catalysts & solvents 2

HCID 178418745HCID 178418745, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The title compound is prepared using an adaptation of the published method of Tamao, et al. Tetrahedron, 1982, 38, 3347-3354. To a THF solution under argon is added 2-Chloro-6,7-dimethoxyquinoxaline (5 g, 26 mmol) and NiCl2(dppp) (0.14 g, 0.26 mmol). The reaction mixture is cooled to 0° C., and a 3 M solution of MeMgBr in Et2O (13 mL, 39 mmol) is added portionwise. The reation mixture is allowed to warm to room temperature, stirred for 1 hour, then refluxed for 1.5 hours. The mixture is cooled, quenched with 10% HCl, stirred 10 minutes, then made basic with 5% NaOH. CH2Cl2 and H2O are added to the reaction, and the mixture stirred overnight. Additional CH2Cl2, H2O, and NaCl are then added and the mixture is filtered. The resulting solution is poured into a separatory funnel, and the aqueous layers are washed 3× with CH2Cl2. The organic layers are combined, washed with brine, dried (MgSO4), concentrated onto silica gel, and chromatographed (50%-80% EtOAc/hexanes) to provide a orange solid (49% yield).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 1.5 hours
  3. temperatureThe mixture is cooled
  4. customquenched with 10% HCl
  5. stirringstirred 10 minutes
  6. additionCH2Cl2 and H2O are added to the reaction
  7. stirringthe mixture stirred overnight
  8. additionAdditional CH2Cl2, H2O, and NaCl are then added
  9. filtrationthe mixture is filtered
  10. additionThe resulting solution is poured into a separatory funnel
  11. washthe aqueous layers are washed 3× with CH2Cl2
  12. washwashed with brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated onto silica gel
  15. customchromatographed (50%-80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e55faf40a6cb4851b5e883c2c6b2b378
Source dataset
uspto-grants-2003_03
Patent number
US06528526B1

Reaction notes

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