Acetic Anhydride → 2-Methylbenzofuran-6-yl acetate

HRID 2261830Notes

Reaction equation

HRID 2261830 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. The crude product is purified by flash chromatography eluted with 25% EtOAc/Hexanes, and the appropriate fractions are concentrated. The material is dissolved in dichloromethane (150 mL) and triethylamine (17.0 mL, 122 mmol) at 0° C. is 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 (10 mL) and concentrated. The residue is purified by silica gel chromatography with 25% EtOAc/Hexanes to provide acetic acid 2-methyl-benzofuran-6-yl ester (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
  5. customThe crude product is purified by flash chromatography
  6. washeluted with 25% EtOAc/Hexanes
  7. concentrationthe appropriate fractions are concentrated
  8. dissolutionThe 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 (10 mL)
  12. concentrationconcentrated
  13. customThe residue is purified by silica gel chromatography with 25% EtOAc/Hexanes

Sources & evidence

ORD record
ord-516c6f34e68341098316f8785e6487e9
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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