5-Bromo-1-benzothiophene → 5-Methoxy-1-benzothiophene

HRID 1387025Notes

Reaction equation

HRID 1387025 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=1.[CH3:11][O-:12].[Na+]>CN(C=O)C.CO>[CH3:11][O:12][C:2]1[CH:10]=[CH:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=1.[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[S:6][CH:7]=[CH:8][C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 27765785-Bromo-1-benzothiopheneHCID 10942334Sodium Methoxide

Product 2

HCID 27765785-Bromo-1-benzothiopheneYield 9.4%HCID 36324255-Methoxy-1-benzothiopheneYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of 1.8 g of 5-bromobenzo[b]thiophene in 2 mL of anhydrous DMF and 1 mL of MeOH was added 686 mg of NaOMe. The mixture was heated to 110° C. (bath temp), and 121 mg of CuBr was added. The brown suspension was heated at 110° C. for ˜2 h and at ˜145° C. for 30 min. The reaction was quenched with ca. 50 mL of H2O and the mixture was extracted with 100 mL of Et2O (2×), EtOAc (1×), and CH2Cl2 (1×). The organic layers were washed with 50 mL of brine, combined, dried over MgSO4, concentrated, and flash chromatographed with 3% Et2O-hexanes to afford 894.5 mg (64%) of the title compound along with 168.8 mg (9.4%) of 5-bromobenzo[b]-thiophene.

Workup

  1. additionwas added
  2. customThe reaction was quenched with ca. 50 mL of H2O
  3. extractionthe mixture was extracted with 100 mL of Et2O (2×), EtOAc (1×), and CH2Cl2 (1×)
  4. washThe organic layers were washed with 50 mL of brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customflash chromatographed with 3% Et2O-hexanes

Sources & evidence

ORD record
ord-2d927ffb5932487f9e796e16da58729a
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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