Tetrahydrofuran → Ethyl 4-cyano-4-(3,4-dichlorophenyl)-6-(t-butyldimethylsilyloxy)hexanoate

HRID 323251Notes

Reaction equation

HRID 323251 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:10]#[N:11])[CH:5]=[CH:6][C:7]=1[Cl:8].O1CCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]>C(OCC)(=O)C.CCCCCC.O>[C:10]([C:9]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:17])[CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])#[N:11]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 68320Ethyl 3-bromopropionateHCID 2733832Lithium HexamethyldisilazideHCID 184647992-(3,4-Dichlorophenyl)-4-(t-butyldimethylsilyloxy)butyronitrile

Product 1

HCID 18464536Ethyl 4-cyano-4-(3,4-dichlorophenyl)-6-(t-butyldimethylsilyloxy)hexanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Combine 2-(3,4-dichlorophenyl)-4-(t-butyldimethylsilyloxy)butyronitrile (13.35 g, 38.8 mmol) and anhydrous tetrahydrofuran (50 mL). Cool in a dry-ice/acetone bath. Add dropwise a solution of lithium bis(trimethylsilyl)amide (42.6 mL, 1 M in THF, 42.6 mmol). Add dropwise, ethyl 3-bromopropionate (7.71 g, 42.6 mmol). Warm the reaction mixture to ambient temperature. After 18 hours, add water. Separate the aqueous layer and extract three times with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 90% ethyl acetate/hexane to give the title compound: Rf=0.35 (silica gel, 10% ethyl acetate/hexane).

Workup

  1. temperatureCool in a dry-ice/acetone bath
  2. additionAdd dropwise
  3. customSeparate the aqueous layer
  4. extractionextract three times with ethyl acetate
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto obtain a residue

Sources & evidence

ORD record
ord-bf1ee93cd3fa473ea644a895aa58d37d
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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