Methyl iodide → 5-Methoxy-2-(4-methoxy-phenyl)-4-methyl-benzofuran

HRID 1836053Notes

Reaction equation

HRID 1836053 reaction equation
Br[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[O:19][CH3:20].[CH2:21]([Li])CCC.CN(CCN(C)C)C.IC>C1COCC1.O>[CH3:20][O:19][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[CH:8][C:7]=2[C:2]=1[CH3:21]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 102152694-Bromo-5-methoxy-2-(4-methoxyphenyl)-benzofuranHCID 178418339Butyllithium

Product 1

HCID 101715395-Methoxy-2-(4-methoxy-phenyl)-4-methyl-benzofuran

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Bromo-5-methoxy-2-(4-methoxyphenyl)-benzofuran 133 (0.282 g, 0.85 mmol) was taken into 20 mL of THF and cooled to 0° C. Then butyllithium (0.68 mL of a 2.5M solution in THF, 1.7 mmol) was added dropwise and allowed to stir for 20 minutes. Then TMEDA (0.256 mL, 1.7 mmol) was added followed by iodomethane (1.06 mL, 17 mmol). The reaction was allowed to stir overnight at room temperature. The reaction was poured into water and extracted with ethyl acetate. The combined organics was washed with water (2×), brine (1×), dried over magnesium sulfate filtered and concentrated. The resulting material was purified by column chromatography on silica gel, using a gradient of 1% to 3% ethyl acetate in hexane. The first fractions contained the product and another side product. This fraction was added to another synthesis of this compound (starting with 0.250 g 4-Bromo-5-methoxy-2-(4-methoxyphenyl)-benzofuran) for the final cleavage reaction.

Workup

  1. stirringto stir overnight at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organics was washed with water (2×), brine (1×)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting material was purified by column chromatography on silica gel
  8. additionThis fraction was added to another synthesis of this compound (starting with 0.250 g 4-Bromo-5-methoxy-2-(4-methoxyphenyl)-benzofuran) for the final
  9. customcleavage reaction

Sources & evidence

ORD record
ord-daebbd3a48624dc99c33657c35f1ed7b
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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