Benzene, (2-iodoethyl)- → 1-Benzoyl-2-(2-phenylethyl)-2-piperidinecarbonitrile

HRID 1781505Notes

Reaction equation

HRID 1781505 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]1[C:23]#[N:24])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH2:25](I)[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1.O>[C:9]([N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C:18]1([CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23]#[N:24])(=[O:16])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 28503Benzene, (2-iodoethyl)-HCID 2724682Lithium diisopropylamideHCID 190288951-Benzoyl-2-piperidinecarbonitrile

Product 1

HCID 190288501-Benzoyl-2-(2-phenylethyl)-2-piperidinecarbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To 200 ml of a solution of lithium diisopropylamide (140 mmol) in tetrahydrofuran was added 15 g of solid 1-benzoyl-2-piperidinecarbonitrile at -78° C. and the mixture was stirred for 30 minutes. Then, 100 ml of a solution of 33.2 g of phenethyl iodide in tetrahydrofuran was added dropwise at -78° C. After completion of dropwise addition, the temperature of the reaction mixture was gradually increased to 0° C. The reaction mixture was diluted with water and the organic layer was separated. The aqueous layer was further extracted with ethyl acetate. The pooled organic layer was dried over magnesium sulfate and filtered and the solvent was distilled off. The group was purified by silica gel column chromatography using ethyl acetate-hexane (1:2) as the eluent. The active fraction was concentrated under reduced pressure and the solid group was recrystallized from ethyl acetate-hexane to provide 17.3 g of colorless crystals.

Workup

  1. additionAfter completion of dropwise addition
  2. customthe organic layer was separated
  3. extractionThe aqueous layer was further extracted with ethyl acetate
  4. dry with materialThe pooled organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. distillationthe solvent was distilled off
  7. customThe group was purified by silica gel column chromatography
  8. concentrationThe active fraction was concentrated under reduced pressure
  9. customthe solid group was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-94dea17c11d546a38a349bc82e649588
Source dataset
uspto-grants-1997_05
Patent number
US05633248

Reaction notes

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