Iodobenzene → HCID 10198654, compound

HRID 354077Notes

Reaction equation

HRID 354077 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[CH:11]=1.C([Li])CCC.I[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[O-]S(C(F)(F)F)(=O)=O.[Cl-].[Li+]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[C:9]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[S:8][C:7]=2[CH:11]=1

Participants

9

Reactant 5

HCID 11575Iodobenzene2×HCID 433294Lithium ChlorideHCID 2758875TrifluoromethanesulfonateHCID 136342376-Methoxy-1-benzothiopheneHCID 178418339Butyllithium

Product 1

HCID 10198654HCID 10198654, compoundYield 68.4%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 6-Methoxy -benzo[b]thiophene (250 mg, 1.52 mmol) in 3.7 mL THF at −20° C. was added dropwise n-butyllithium (0.67 mL, 1.67 mmol). The mixture was stirred at 0° C. for 1.5 hrs. and at room temperature for 0.5 hrs. Anhydrous zinc chloride (269 mg, 1.97 mmol) in 1.9 mL of THF was added by cannula to the reaction. The reaction was then stirred at room temperature for 15 minutes and then Pd(Ph3P)4 (70 mg, 0.06 mmol) and iodobenzene (0.22 mL, 1.97 mmol) were added and the reaction stirred at room temperature for 3 hrs. Other aromatic or heteroaromatic bromides, iodides or triflates can replace iodobenzene in this procedure. If a triflate is used 3 equivalents of anhydrous lithium chloride must be added. The reaction can be refluxed overnight to push it towards completion. The solvent was evaporated and the residue was diluted water and extracted into ethyl acetate. The combined organic layers was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was chromatographed on silica gel using 100% Hexanes to 1% ethyl acetate/hexanes as the gradient eluant to yield 250 mg of the title compound.

Workup

  1. waitand at room temperature for 0.5 hrs
  2. stirringThe reaction was then stirred at room temperature for 15 minutes
  3. stirringthe reaction stirred at room temperature for 3 hrs
  4. additionmust be added
  5. customThe reaction
  6. temperaturecan be refluxed overnight
  7. customThe solvent was evaporated
  8. extractionextracted into ethyl acetate
  9. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was chromatographed on silica gel using 100% Hexanes to 1% ethyl acetate/hexanes as the gradient eluant

Sources & evidence

ORD record
ord-0122147bf8c643e19df17ff3e1143cec
Source dataset
uspto-grants-2004_06
Patent number
US06756388B1

Reaction notes

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