Tetrahydrofuran → 2-(4-Bromo-3,5-dimethoxyphenyl)furan

HRID 2359164Notes

Reaction equation

HRID 2359164 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](I)[CH:6]=[C:7]([O:10][CH3:11])[C:8]=1[Br:9].[O:13]1[CH:17]=[CH:16][CH:15]=[C:14]1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1COCC1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Br:9][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]([C:14]2[O:13][CH:17]=[CH:16][CH:15]=2)=[CH:6][C:7]=1[O:10][CH3:11]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 2734357Furan-2-boronic acidHCID 584320782-Bromo-5-iodo-1,3-dimethoxybenzene

Product 1

HCID 584319882-(4-Bromo-3,5-dimethoxyphenyl)furanYield 91.2%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

2-(4-Bromo-3,5-dimethoxyphenyl)furan was synthesized according to the procedure reported in WO 2008/040669 as follows. To a round bottom flask containing 3,5-dimethoxy-4-bromo-iodobenzene (7.9 g, 85% purity, 19.6 mmol), 2-furylboronic acid (3.4 g, 30.4 mmol), triphenylphosphine (0.358 g, 1.37 mmol), tetrabutylammonium bromide (7.94 g, 14.6 mmol) and Na2CO3 (4.9 g, 46.2 mmol) was added THF (87 mL) and H2O (87 mL). The mixture was degassed by alternately putting under house vacuum and argon three times for several minutes each. 10% Pd/C (1.36 g) was added and the mixture was heated at 60° C. for 17 hrs under argon. After cooling to room temperature, the mixture was filtered through Celite and rinsed with THF and EtOAc. The filtrate layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated. Purification by column chromatography (0-25% Et2O-hexanes) gave 2-(4-bromo-3,5-dimethoxyphenyl)furan as a white solid (5.06 g, 91% yield). Product TLC Rf 0.35 (15% EtOAc-hexanes TLC eluent).

Workup

  1. custom2-(4-Bromo-3,5-dimethoxyphenyl)furan was synthesized
  2. customThe mixture was degassed
  3. waitby alternately putting under house vacuum and argon three times for several minutes
  4. addition10% Pd/C (1.36 g) was added
  5. temperatureAfter cooling to room temperature
  6. filtrationthe mixture was filtered through Celite
  7. washrinsed with THF and EtOAc
  8. customThe filtrate layers were separated
  9. washthe organic layer was washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customPurification by column chromatography (0-25% Et2O-hexanes)

Sources & evidence

ORD record
ord-0e987013cf5a4471b76578cb9c33e078
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

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