Acetone → 3-Methyl-1-phenyl-3-[(trimethylsilyl)oxy]butan-1-one

HRID 1406606Notes

Reaction equation

HRID 1406606 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:11])[CH3:10].[CH3:18][C:19]([CH3:21])=[O:20].N1C=CN=C1.Cl[Si:28]([CH3:31])([CH3:30])[CH3:29]>CCCCCCC.O.CN(C=O)C.C1COCC1>[CH3:18][C:19]([O:20][Si:28]([CH3:31])([CH3:30])[CH3:29])([CH3:21])[CH2:10][C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11]

Participants

10

Reactant 5

HCID 180AcetoneHCID 795ImidazoleHCID 6397ChlorotrimethylsilaneHCID 7410AcetophenoneHCID 2724682Lithium diisopropylamide

Product 1

HCID 151514373-Methyl-1-phenyl-3-[(trimethylsilyl)oxy]butan-1-one

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

A flask is charged with THF (1 L), cooled to −50° C., and treated with lithium diisopropylamide (LDA) (1.05 L, 1.89 mol, 1.1 equiv, 1.8M in THF/heptane/ethylbenzene). The reactor contents are then treated with acetophenone (200 mL, 1.71 mol, 1.0 equiv) at a rate to maintain the batch at about −50° C. The reaction mixture is stirred at about −50° C. for 30 minutes then treated with acetone (151 mL, 2.06 mol, 1.2 equiv) at a rate to maintain the mixture at about −50° C. The reaction mixture is stirred at about −50° C. for 1 hour then treated with water (1 L) and heptane (500 mL). The reaction mixture is allowed to warm to 25° C., and the resultant organic phase is collected and washed with water (400 mL). The organic phase is concentrated to an oil and treated with a solution of imidazole (233.4 g, 3.43 mol, 2.0 equiv) and DMF (600 mL). The resultant solution is treated with chlorotrimethylsilane (217.6 mL, 1.71 mol, 1.0 equiv) at a rate to maintain the reaction mixture at no more than 35° C. The reaction mixture is stirred at 25° C. for 1 hour, and diluted with heptane (600 mL) and water (1 L). The resultant organic phase is collected, washed with water (3×500 mL), and concentrated. The resultant oil is then vacuum distilled at 1-3 mm Hg (product distills at 83-88° C.) to provide 2 as a yellow liquid. Yield: 160.3 g, 37%.

Workup

  1. temperatureto maintain the batch at about −50° C
  2. temperatureto maintain the mixture at about −50° C
  3. stirringThe reaction mixture is stirred at about −50° C. for 1 hour
  4. temperatureto warm to 25° C.
  5. customthe resultant organic phase is collected
  6. washwashed with water (400 mL)
  7. concentrationThe organic phase is concentrated to an oil
  8. temperatureto maintain the reaction mixture at no more than 35° C
  9. stirringThe reaction mixture is stirred at 25° C. for 1 hour
  10. customThe resultant organic phase is collected
  11. washwashed with water (3×500 mL)
  12. concentrationconcentrated
  13. distillationvacuum distilled at 1-3 mm Hg (product distills at 83-88° C.)

Sources & evidence

ORD record
ord-e17f6e93f7564f6c8d2e1c050fca48c6
Source dataset
uspto-grants-2014_12
Patent number
US08916701B2

Reaction notes

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