Phenylacetonitrile → 3-[4-(Tert-butyldimethylsilyloxymethyl)phenyl]-2-phenylpropanonitrile

HRID 2399461Notes

Reaction equation

HRID 2399461 reaction equation
[C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(P(N(C)C)(N(C)C)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])=[CH:35][CH:34]=1>C1COCC1>[Si:41]([O:40][CH2:39][C:36]1[CH:35]=[CH:34][C:33]([CH2:32][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]#[N:9])=[CH:38][CH:37]=1)([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:42])[CH3:43]

Participants

6

Reactant 4

HCID 8794PhenylacetonitrileHCID 12679HexamethylphosphoramideHCID 2733832Lithium HexamethyldisilazideHCID 10757711{[4-(Bromomethyl)phenyl]methoxy}(tert-butyl)dimethylsilane

Product 1

HCID 193856503-[4-(Tert-butyldimethylsilyloxymethyl)phenyl]-2-phenylpropanonitrileYield 67.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of phenylacetonitrile (1.5 mL, 12.7 mmol) in THF (40 mL) containing HMPA (11 mL, 63.4 mmol) was cooled to -78° C. and treated with 16 mL (16 mmol) of a 1.0M THF solution of lithium bis(trimethylsilyl)amide dropwise while the temperature was maintained at -78° C. The reaction was stirred at -78° C. for 1.5 hours, and a solution of the product of Step B (2.00 g, 6.34 mmol) in THF (8 mL) was added dropwise with the temperature maintained below -70° C. The reaction temperature was maintained below -68° C. for 3 hours. The reaction was quenched at this temperature by addition of 1N Na2HSO4. After warming to room temperature, the mixture was partitioned between EtOAc and water, and the combined organic layers were washed with water, saturated NaHCO3, brine, dried (MgSO4), filtered, then concentrated in vacuo. The residue was chromatographed on a silica gel flash chromatography column eluted with 5% ethyl acetate/hexane to afford 1.5 g (67%) of the title compound.

Workup

  1. temperaturewas maintained at -78° C
  2. temperaturemaintained below -70° C
  3. temperatureThe reaction temperature was maintained below -68° C. for 3 hours
  4. customThe reaction was quenched at this temperature by addition of 1N Na2HSO4
  5. temperatureAfter warming to room temperature
  6. customthe mixture was partitioned between EtOAc and water
  7. washthe combined organic layers were washed with water, saturated NaHCO3, brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was chromatographed on a silica gel flash chromatography column
  12. washeluted with 5% ethyl acetate/hexane

Sources & evidence

ORD record
ord-7e853215bdc242eeb1955aae70049f5f
Source dataset
uspto-grants-1995_09
Patent number
US05449682

Reaction notes

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