Ethyl Acetate → 8-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-methoxymethoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

HRID 215816Notes

Reaction equation

HRID 215816 reaction equation
Br[C:2]1[C:11]([CH2:12][O:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[CH3:21])=[C:10]2[C:5]([NH:6][C:7]([CH3:25])([CH3:24])[C:8](=[O:23])[N:9]2[CH3:22])=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[C:32]([O:34][CH2:35][O:36][CH3:37])[CH:31]=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O>[F:20][C:18]1[CH:17]=[CH:16][C:15]([CH3:21])=[C:14]([CH:19]=1)[O:13][CH2:12][C:11]1[C:2]([C:29]2[CH:30]=[CH:31][C:32]([O:34][CH2:35][O:36][CH3:37])=[CH:33][C:28]=2[O:27][CH3:26])=[CH:3][CH:4]=[C:5]2[C:10]=1[N:9]([CH3:22])[C:8](=[O:23])[C:7]([CH3:25])([CH3:24])[NH:6]2

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 108892012-Methoxy-4-methoxymethoxyphenylboronic acidHCID 247811517-Bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 583371898-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-methoxymethoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-oneYield 97%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Under argon atmosphere, a mixture of 7-bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 3-1, 2.32 g, 5.70 mmol), 2-methoxy-4-methoxymethoxyphenylboronic acid (Reference Compound No. 7-1, 2.43 g, 11.5 mmol), cesium carbonate (9.46 g, 29.0 mmol), and bis(triphenylphosphine)palladium(II)dichloride (415 mg, 0.591 mmol) was suspended in anhydrous N,N-dimethylformamide (25 ml) and the mixture was stirred at 80° C. for 5 hours. After cooling down, ethyl acetate (150 mL) and water (150 mL) were added and partitioned. The organic layer was washed with saturated brine (150 mL), dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (2.73 g) as a colorless solid. (Yield 97%)

Workup

  1. temperatureAfter cooling down
  2. custompartitioned
  3. washThe organic layer was washed with saturated brine (150 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a157759ea0ac468ba2488c39debde349
Source dataset
uspto-grants-2012_06
Patent number
US08193187B2

Reaction notes

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