Dimethylformamide → 6-(benzyloxy)-2,2-dimethylbenzofuran-3(2H)-one

HRID 645050Notes

Reaction equation

HRID 645050 reaction equation
[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:12]2[C:13](=O)[CH2:14][O:15][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:22].CN([CH:26]=[O:27])C>>[CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:12]2[C:26](=[O:27])[C:14]([CH3:13])([CH3:22])[O:15][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 106337743(2H)-Benzofuranone, 6-(phenylmethoxy)-

Product 1

HCID 666425186-(benzyloxy)-2,2-dimethylbenzofuran-3(2H)-oneYield 47%

Procedure

To a solution of 6-(benzyloxy)benzofuran-3(2H)-one (Adams, J. L., et al., J. Med. Chem. (1996), 39(26):5035-46) (1.60 g, 6.67 mmol) in DMF (50.0 mL) were added sodium hydride (0.59 g, 14.7 mmol) and iodomethane (1.46 mL, 23.3 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h and quenched with saturated ammonium chloride (50.0 mL). The aqueous mixture was extracted with ethyl acetate (3×50.0 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/10) to give the title compound (0.85 g, 47%): 1H NMR (300 MHz, CDCl3) δ 7.55 (d, 1H), 7.44-7.30 (m, 5H), 6.69 (dd, 1H), 6.54 (d, 1H), 5.10 (s, 2H), 1.43 (s, 6H); MS (ES+) m/z 269.5 (M+1).

Workup

  1. customquenched with saturated ammonium chloride (50.0 mL)
  2. extractionThe aqueous mixture was extracted with ethyl acetate (3×50.0 mL)
  3. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-0dbc4901aa4e426e80316d5c7b0e46f6
Source dataset
uspto-grants-2010_04
Patent number
US07700641B2

Reaction notes

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