4-Nitrophenol → 5-Acetoxy-4,6-di-t-butyl-2-methyl-2-(4-nitrophenoxymethyl)-2,3-dihydrobenzofuran

HRID 367312Notes

Reaction equation

HRID 367312 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].[C:13]([O:16][C:17]1[C:18]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:19][C:20]2[O:24][C:23]([CH2:26]I)([CH3:25])[CH2:22][C:21]=2[C:28]=1[C:29]([CH3:32])([CH3:31])[CH3:30])(=[O:15])[CH3:14].[Cl-].[NH4+]>CN(C)C=O>[C:13]([O:16][C:17]1[C:18]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:19][C:20]2[O:24][C:23]([CH3:25])([CH2:26][O:10][C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:22][C:21]=2[C:28]=1[C:29]([CH3:32])([CH3:31])[CH3:30])(=[O:15])[CH3:14]

Participants

6

Reactant 4

HCID 9804-NitrophenolHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 154857225-Acetoxy-4,6-di-t-butyl-2-iodomethyl-2-methyl-2,3-dihydrobenzofuran

Product 1

HCID 232880295-Acetoxy-4,6-di-t-butyl-2-methyl-2-(4-nitrophenoxymethyl)-2,3-dihydrobenzofuranYield 64.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Under a nitrogen atmosphere, a solution of 3.76 g of 4-nitrophenol in 25 ml of N,N-dimethylformamide was added dropwise to an ice-cooled suspension of 1.08 g of 60% oily sodium hydride in 50 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 1 hour. Then, the reaction solution was cooled to 0° C. and a solution of 10 g of 5-acetoxy-4,6-di-t-butyl-2-iodomethyl-2-methyl-2,3-dihydrobenzofuran synthesized in Example 70-2) in 25 ml of N,N-dimethylformamide was added dropwise, and the mixture was heated under reflux for 14 hours. After cooling, the reaction solution was combined with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated. The concentrate was purified by silica gel column chromatography eluting with n-hexane containing 20% ethyl acetate to give 6.57 g of 5-acetoxy-4,6-di-t-butyl-2-methyl-2-(4-nitrophenoxymethyl)-2,3-dihydrobenzofuran (rotamer mixture) as a pale yellow oil (yield 64%).

Workup

  1. temperaturecooled
  2. temperatureThen, the reaction solution was cooled to 0° C.
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 14 hours
  5. temperatureAfter cooling
  6. extractionextracted with ethyl acetate
  7. washthe organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customThe concentrate was purified by silica gel column chromatography
  11. washeluting with n-hexane containing 20% ethyl acetate

Sources & evidence

ORD record
ord-b5cf9b0c1e0f479bb198c4f670cbde4b
Source dataset
uspto-grants-2000_10
Patent number
US06133279

Reaction notes

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