(4-Methoxyphenyl)boronic acid → 7-(4-Methoxyphenyl)benzo[b]thiophene

HRID 1372148Notes

Reaction equation

HRID 1372148 reaction equation
[F-].[K+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.Br[C:15]1[C:23]2[S:22][CH:21]=[CH:20][C:19]=2[CH:18]=[CH:17][CH:16]=1>C1COCC1.CCOCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].P(C1CCCCC1)(C1CCCCC1)C1CCCCC1.B(O)O>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:15]2[C:23]3[S:22][CH:21]=[CH:20][C:19]=3[CH:18]=[CH:17][CH:16]=2)=[CH:7][CH:6]=1

Participants

9

Reactant 3

HCID 201262(4-Methoxyphenyl)boronic acidHCID 522689Potassium FluorideHCID 120455387-Bromobenzo[b]thiophene

Product 1

HCID 210717947-(4-Methoxyphenyl)benzo[b]thiopheneYield 97.6%

Reagents, catalysts & solvents 5

HCID 61668Boronic AcidCatalystHCID 75806TricyclohexylphosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a 50 ml round bottom flask was added Pd2(dba)3 (107 mg, 0.117 mmol), KF (2.25 g, 3.9 mmol), 4-methoxyphenylboronic acid (2.14 g, 14.1 mmol), and the flask was purged with nitrogen. Anhydrous THF (25 ml) was then added followed by 7-bromo-1-benzothiophene (2.5 g, 11.73 mmol) in 5 ml THF followed by the addition of P(Cy)3 (100 mg, 0.352 mmol). After 4 h at ambient temperature no product was observed. Heating to 60° C. overnight afforded approx. 50% completion. After the addition of another 2% Pd2(dba)3 (215 mg), 0.1 equivalent boronic acid (26 mg) and THF, the reaction was complete in 2 h. The reaction was cooled, diluted with ether, filtered through a silica plug and concentrated to 3.33 g amber oil. Purification by column chromatography (load: 5% EtOAc/hexanes to 10% EtOAc/hexanes) afforded 2.75 g (97.5%) product as a light yellow solid: mp 74–75° C.; 1H NMR (300 MHz, DMSO-d6): δ 3.84 (3H, s), 7.11 (2H, d, J=8.7 Hz), 7.37 (1H, d, J=7.1 Hz), 7.48 (1H, t, J=7.6 Hz), 7.54 (1H, d, J=5.5 Hz), 7.67 (2H, d, J=8.7 Hz), 7.79 (1H, d, J=5.5 Hz), 7.86 (1H, dd, J=7.4 Hz, 0.8 Hz); MS (ESI) m/z 239 ([M−H]).

Workup

  1. customthe flask was purged with nitrogen
  2. additionAnhydrous THF (25 ml) was then added
  3. customafforded approx. 50% completion
  4. waitthe reaction was complete in 2 h
  5. temperatureThe reaction was cooled
  6. filtrationfiltered through a silica plug
  7. concentrationconcentrated to 3.33 g amber oil
  8. customPurification by column chromatography (load: 5% EtOAc/hexanes to 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7ea3cb282c0642e4af24af70667a5dd7
Source dataset
uspto-grants-2007_01
Patent number
US07157491B2

Reaction notes

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