Methyl iodide → 5-fluoro-1-methyl-3,4-dihydroquinoxalin-2(1H)-one

HRID 558976Notes

Reaction equation

HRID 558976 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][CH2:5][C:6](=[O:12])[NH:7]2.[H-].[Na+].I[CH3:16]>C1COCC1.[Cl-].[Na+].O>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][CH2:5][C:6](=[O:12])[N:7]2[CH3:16]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 229128785-Fluoro-1,2,3,4-tetrahydroquinoxalin-2-one

Product 1

HCID 231111055-fluoro-1-methyl-3,4-dihydroquinoxalin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 5-fluoro-3,4-dihydro-1H-quinoxalin-2-one from Example B (415 mg, 2.5 mmol) in THF (10 ml) was added sodium hydride (60%, 100 mg, 2.5 mmol) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature and stirred for 0.5 h. The mixture was cooled again in an ice/water bath and iodomethane (156 μl, 2.5 mmol) was added. The mixture was allowed to warm slowly to room temperature and stirred for 3 days. Brine was added and the mixture was evaporated in vacuo. The residue was partitioned between EtOAc and brine and separated. The organic phase was washed with brine, dried and evaporated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet ether 45:55) to give a white solid; yield 210 mg, 47%.

Workup

  1. temperaturewhile cooling in an ice/water bath
  2. temperatureThe mixture was cooled again in an ice/water bath
  3. temperatureto warm slowly to room temperature
  4. stirringstirred for 3 days
  5. customthe mixture was evaporated in vacuo
  6. customThe residue was partitioned between EtOAc and brine
  7. customseparated
  8. washThe organic phase was washed with brine
  9. customdried
  10. customevaporated in vacuo
  11. customThe residue was purified by flash chromatography on silica (eluant EtOAc:pet ether 45:55)
  12. customto give a white solid

Sources & evidence

ORD record
ord-b3791ab77eb9413f9a3ea64b82a8f210
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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