Acetic Anhydride → 2-Methylbenzofuran-6-yl acetate

HRID 250260Notes

Reaction equation

HRID 250260 reaction equation
COC1[CH:12]=[CH:11][C:6]2[CH:7]=[C:8]([CH3:10])[O:9][C:5]=2C=1.B(Br)(Br)Br.C(N(CC)CC)C.[C:24]([O:27][C:28](=O)[CH3:29])(=[O:26])[CH3:25]>ClCCl>[CH3:10][C:8]1[O:9][C:5]2[CH:29]=[C:28]([O:27][C:24](=[O:26])[CH3:25])[CH:12]=[CH:11][C:6]=2[CH:7]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 25134Boron tribromideHCID 130130736-Methoxy-2-methylbenzofuran

Product 1

HCID 221435562-Methylbenzofuran-6-yl acetateYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-methoxy-2-methyl-benzofuran (17.4 g, 107 mmol) in dichloromethane (200 mL) at 0° C. is treated with boron tribromide (1.0 M, 107 mL). The mixture is stirred at 0° C. for 60 minutes and quenched with water (50 mL). The organic layer is dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified by flash chromatography eluting with 25% EtOAc/Hexanes. The appropriate fractions are concentrated under reduced pressure. The resulting material is dissolved in dichloromethane (150 mL) and triethylamine (17.0 mL, 122 mmol) at 0° C. and treated with acetic acid anhydride (7.22 mL, 76.35 mmol). The reaction is stirred for 16 hours and allowed to warm to room temperature. The reaction is quenched with MeOH (100 mL) and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with 25% EtOAc/Hexanes to provide the title compound (9.50 g, 82%). 1H NMR (400 MHz, CDCl3): δ 7.40-7.38 (d, 1H), 7.15 (s, 1H), 6.91-6.88 (d, 1H), 6.32 (s, 1H), 2.41 (s, 3H), 2.29 (s, 3H).

Workup

  1. customquenched with water (50 mL)
  2. dry with materialThe organic layer is dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is purified by flash chromatography
  6. washeluting with 25% EtOAc/Hexanes
  7. concentrationThe appropriate fractions are concentrated under reduced pressure
  8. dissolutionThe resulting material is dissolved in dichloromethane (150 mL)
  9. stirringThe reaction is stirred for 16 hours
  10. temperatureto warm to room temperature
  11. customThe reaction is quenched with MeOH (100 mL)
  12. concentrationconcentrated under reduced pressure
  13. customThe residue is purified by silica gel chromatography
  14. washeluting with 25% EtOAc/Hexanes

Sources & evidence

ORD record
ord-cfff160a32454cdc9efbef3223705110
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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