Acetone → 1-(3,5-Di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-3-methyl-butan-1-one

HRID 2260171Notes

Reaction equation

HRID 2260171 reaction equation
[CH3:1][C:2]([C:4]1[CH:9]=[C:8]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:7]([OH:14])=[C:6]([C:15]([CH3:18])([CH3:17])[CH3:16])[CH:5]=1)=[O:3].C(N(C(C)C)CC)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[CH3:40][C:41]([CH3:43])=[O:42]>C(Cl)Cl>[C:15]([C:6]1[CH:5]=[C:4]([C:2](=[O:3])[CH2:1][C:41]([OH:42])([CH3:43])[CH3:40])[CH:9]=[C:8]([C:10]([CH3:11])([CH3:13])[CH3:12])[C:7]=1[OH:14])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 180AcetoneHCID 65367Trimethylsilyl triflateHCID 81531DiisopropylethylamineHCID 6162963',5'-Bis(tert-butyl)-4'-hydroxyacetophenone

Product 1

HCID 99265721-(3,5-Di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-3-methyl-butan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 3,5-di-tert-butyl-4-hydroxyacetophenone (Apim Chemicals, Ltd.) (4 g) in dry methylene chloride (250 mL) is cooled to -78° C. and di-isopropyl ethylamine (7.3 mL) is added followed by trimethylsilyl trifluoromethanesulphonate (Aldrich Chemical Co.) (8.0 mL). The mixture is stirred at -78° C. for 10 minutes and is allowed to warm to ambient temperature over 1 hour. The mixture is cooled again to -78° C. and dry acetone (4.05 mL) is added dropwise. After stirring for 25 minutes, the mixture is washed with 1N aqueous hydrochloric acid and brine. The organic solution is dried over anhydrous sodium sulfate and the solvent is removed under reduced pressure. The crude product is dissolved in methanol-1N aqueous HCl mixture (10:1, v/v, 200 mL) and the homogenous solution is stirred for 1 hour at room temperature. Methanol is removed under reduced pressure; the mixture is washed with methylene chloride. The organic extracts are washed: with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, and the solvent is removed under reduced pressure. The crude product is crystallized from hexane to give 1-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-3-methyl-butan-1-one as orange crystals. Two additional crystallizations give product of analytical purity, mp 113°-14° C.

Workup

  1. temperatureto warm to ambient temperature over 1 hour
  2. temperatureThe mixture is cooled again to -78° C.
  3. stirringAfter stirring for 25 minutes
  4. washthe mixture is washed with 1N aqueous hydrochloric acid and brine
  5. dry with materialThe organic solution is dried over anhydrous sodium sulfate
  6. customthe solvent is removed under reduced pressure
  7. dissolutionThe crude product is dissolved in methanol-1N aqueous HCl mixture (10:1, v/v, 200 mL)
  8. stirringthe homogenous solution is stirred for 1 hour at room temperature
  9. customMethanol is removed under reduced pressure
  10. washthe mixture is washed with methylene chloride
  11. washThe organic extracts are washed
  12. dry with materialwith aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate
  13. customthe solvent is removed under reduced pressure
  14. customThe crude product is crystallized from hexane

Sources & evidence

ORD record
ord-4c33721122104836a4f6d209b869d6c2
Source dataset
uspto-grants-1995_12
Patent number
US05476876

Reaction notes

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