Acetyl chloride → N-[3-(4-Isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl]-N-[2-(4-methoxyphenyl)ethyl]acetamide

HRID 272372Notes

Reaction equation

HRID 272372 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:32])=[C:16]([NH:21][CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2([CH3:34])[CH3:33])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[C:35](Cl)(=[O:37])[CH3:36].C(=O)([O-])O.[Na+]>CCCCCC.C(OCC)(=O)C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[C:14]3[C:15]([CH3:32])=[C:16]([N:21]([CH2:22][CH2:23][C:24]4[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=4)[C:35](=[O:37])[CH3:36])[C:17]([CH3:20])=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2([CH3:34])[CH3:33])=[CH:8][CH:9]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 9933828HCID 9933828, compound

Product 1

HCID 10185352N-[3-(4-Isopropylphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl]-N-[2-(4-methoxyphenyl)ethyl]acetamideYield 46%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
60 °C

Procedure

Sodium hydride (a 60% dispersion in liquid paraffin, 232.1 mg, 5.80 mmol) was washed twice with hexane and then suspended to N,N-dimethylformamide (25 ml). To this suspension was added under an argon atmosphere 3-(4-isopropylphenyl)-N-[2-(4-methoxyphenyl)ethyl]-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-amine (537.9 mg, 1.18 mmol) and the reaction mixture was stirred at 60° C. for 20 minutes. Then, acetyl chloride (0.5 ml, 7.03 mmol) was added into the reaction mixture and stirred at the same temperature for 1 hour. After the reaction solution was cooled down to room temperature, an aqueous saturated solution of sodium hydrogen carbonate was added to the reaction mixture and the product was extracted twice with ethyl acetate. The combined extracts were washed with water, dried on magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography on silica gel (hexane-ethyl acetate 3:1) to obtain the rotamer 1 (Rf=0.38; hexane-ethyl acetate 3:1) of the title compound (46% yield). Melting point: 134-136° C. (Ethyl acetate-hexane)

Workup

  1. washSodium hydride (a 60% dispersion in liquid paraffin, 232.1 mg, 5.80 mmol) was washed twice with hexane
  2. stirringstirred at the same temperature for 1 hour
  3. temperatureAfter the reaction solution was cooled down to room temperature
  4. extractionthe product was extracted twice with ethyl acetate
  5. washThe combined extracts were washed with water
  6. customdried on magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7a1ce7aded7345f1becc9e529509f793
Source dataset
uspto-grants-2008_11
Patent number
US07456162B2

Reaction notes

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