Tetrahydrofuran → 2-(3,4-Dichlorophenyl)-4-(t-butyldimethylsilyloxy)butyronitrile

HRID 323250Notes

Reaction equation

HRID 323250 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8].O1CCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Si:27]([O:34][CH2:35][CH2:36]Br)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]>C(OCC)(=O)C.CCCCCC>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:36][CH2:35][O:34][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 76690(3,4-Dichlorophenyl)acetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane2×

Product 1

HCID 184647992-(3,4-Dichlorophenyl)-4-(t-butyldimethylsilyloxy)butyronitrile

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Combine 3,4-dichlorophenylacetonitrile (10 g, 53.8 mmol) and anhydrous tetrahydrofuran (50 mL). Cool in a dry-ice/acetone bath. Add dropwise a solution of lithium bis(trimethylsilyl)amide (64.5 mL, 1 M in THF, 64.5 mmol). Add dropwise, 2-(t-butyldimethylsilyloxy)-1-bromoethane (15.43 g, 64.5 mmol). When the addition of 2-(t-butyldimethylsilyloxy)-1-bromoethane is complete, warm the reaction mixture to ambient temperature. After 12 hours, partition the reaction mixture between ethyl acetate and water. Extract the aqueous layer twice with ethyl acetate. Combine the organic layers and extract with 1 M hydrochloric acid solution, dry over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 10% ethyl acetate/hexane to give the title compound: Rf=0.42 (silica gel, 10% ethyl acetate/hexane).

Workup

  1. temperatureCool in a dry-ice/acetone bath
  2. additionAdd dropwise
  3. custompartition the reaction mixture between ethyl acetate and water
  4. extractionExtract the aqueous layer twice with ethyl acetate
  5. extractionextract with 1 M hydrochloric acid solution
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customto obtain a residue

Sources & evidence

ORD record
ord-c971ae9e325f47bc94ecc69fbf68c0ca
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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