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

HRID 1038491Notes

Reaction equation

HRID 1038491 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][C:35]([F:38])([F:37])[F:36])[CH:31]=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].C(OCC)(=O)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.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][C:35]([F:37])([F:38])[F:36])=[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 19660Carbonate IonHCID 22490042(2-Methoxy-4-(trifluoromethoxy)phenyl)boronic acidHCID 247811517-Bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 576719048-(5-Fluoro-2-methylphenoxymethyl)-7-(2-methoxy-4-trifluoromethoxyphenyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-oneYield 83.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-bromo-8-(5-fluoro-2-methylphenoxymethyl)-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 8-1, 49.7 mg, mmol), 2-methoxy-4-trifluoromethoxyphenylboronic acid (58.1 mg, 0.246 mmol), cessium carbonate (119 mg, 0.36 mmol) and bis(triphenylphosphin)palladium (II) dichloride (12.0 mg, 0.0171 mmol) was suspended in anhydrous N,N-dimethylformamide (0.5 ml) and stirred at 80° C. for 2 hours under argon atomosphere. After cooling down, ethyl acetate (100 mL) and water (100 mL) was added and partitioned. The organic layer was washed with saturated brine (50 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 compound (52.7 mg) as a colorless amorphous product. (Yield 58%)

Workup

  1. temperatureAfter cooling down
  2. custompartitioned
  3. washThe organic layer was washed with saturated brine (50 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-b051aac8d18546b9be61ee08efe55b26
Source dataset
uspto-grants-2013_10
Patent number
US08551991B2

Reaction notes

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