Ethyl Acetate → 4-[4-(Tert-butyldimethylsiloxy)piperidin-1-yl]benzonitrile

HRID 856028Notes

Reaction equation

HRID 856028 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[O:10]([CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].CC(C)([O-])C.[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:10]([CH:18]1[CH2:23][CH2:22][N:21]([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH2:20][CH2:19]1)[Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 12162Benzonitrile, 4-bromo-HCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 694805284-[4-(Tert-butyldimethylsiloxy)piperidin-1-yl]benzonitrileYield 66%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromobenzonitrile (2.76 g, 15.16 mmol), 4-(tert-butyldimethylsiloxy)piperidine (2.9 g, 13.79 mmol), palladium acetate (62 mg, 0.28 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (258 mg, 0.41 mmol), and sodium tert-butoxide (1.99 g, 20.68 mmol) in toluene (60 ml) was stirred at 80° C. for 1 hour. The reaction mixture was allowed to return to room temperature, to which ethyl acetate (60 ml) was added, and the mixture was filtered. The filtration was washed with water and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/methylene chloride=1/1) to afford 4-[4-(tert-butyldimethylsiloxy)piperidin-1-yl]benzonitrile (2.8 g, yield 66%) as a pale yellow crystalline powder.

Workup

  1. additionwas added
  2. filtrationthe mixture was filtered
  3. filtrationThe filtration
  4. washwas washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (n-hexane/methylene chloride=1/1)

Sources & evidence

ORD record
ord-b2a554d3b81b49d48178e13bc701e6cc
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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