Sodium Carbonate → 5-Bromo-8-(3,5-dimethoxy-phenyl)-quinoxaline

HRID 43216Notes

Reaction equation

HRID 43216 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.Br[C:15]1[CH:24]=[CH:23][C:22]([Br:25])=[C:21]2[C:16]=1[N:17]=[CH:18][CH:19]=[N:20]2.C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:25][C:22]1[CH:23]=[CH:24][C:15]([C:5]2[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=2)=[C:16]2[C:21]=1[N:20]=[CH:19][CH:18]=[N:17]2

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 115147635,8-Dibromoquinoxaline

Product 1

HCID 592928255-Bromo-8-(3,5-dimethoxy-phenyl)-quinoxalineYield 70.7%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 3,5-dimethoxyphenylboronic acid (3.38 g, 18.6 mmol) in EtOH (15 mL) was added dropwise to a mixture of 5,8-dibromo-quinoxaline (Step 179.5) (10.7 g, 37.1 mmol, 2 equiv), PdCl2(dppf) (530 mg, 0.7 mmol, 0.03 equiv), Na2CO3 (2 M solution in H2O, 37 mL, 74.3 mmol, 4 equiv) in toluene (100 mL) at 105° C., under an argon atmosphere. The reaction mixture was stirred at 105° C. for 2 h, allowed to cool to rt, diluted with EtOAc and H2O, filtered through a pad of celite and extracted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by trituration in DCM, followed by silica gel column chromatography (Hex/EtOAc, 4:1) to afford 4.54 g of the title compound as a yellow solid: ES-MS: 345 [M+H]+; tR=5.13 min (System 1); Rf=0.17 (Hex/EtOAc, 4:1).

Workup

  1. temperatureto cool to rt
  2. filtrationfiltered through a pad of celite
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by trituration in DCM

Sources & evidence

ORD record
ord-fd9dcd28be8e4f8e96de3408ed8648a5
Source dataset
uspto-grants-2013_09
Patent number
US08536175B2

Reaction notes

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