Acetonitrile → HCID 22265419, compound

HRID 489443Notes

Reaction equation

HRID 489443 reaction equation
[C:1](#[N:3])[CH3:2].[Li]CCCC.[C:9]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20]CC)=O)[CH2:14][CH2:13]1)(=[O:11])[CH3:10]>C1COCC1>[C:9]([N:12]1[CH2:13][CH2:14][CH:15]([C:18](=[O:20])[CH2:2][C:1]#[N:3])[CH2:16][CH2:17]1)(=[O:11])[CH3:10]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 690430Ethyl 1-acetylpiperidine-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 22265419HCID 22265419, compoundYield 76.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl isonipecotate (8.0 g) in THF (100 mL) was added triethylamine (5.7 g), dimethylaminopyridine (0.6 g) and acetyl chloride (4.4 g) at 0° C. and the mixture was stirred for an hour. The mixture was extracted with ethyl acetate and the solvent was evaporated under reduced pressure to give ethyl 1-acetylpiperidine-4-carboxylate (10 g) as a colorless oil. To a solution of acetonitrile (2.5 g) in THF (300 mL) was added n-BuLi (57 mmol) at −78° C. Further, ethyl 1-acetylpiperidine-4-carboxylate (10 g) was added and the mixture was stirred for an hour. After acidification with hydrochloric acid, the mixture was extracted with ethyl acetate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1)) to give 1-(1-acetylpiperidin-4-yl)-2-cyanoethan-1-one (7.5 g) as a colorless oil. A solution of 2,1,3-benzoxadiazole-4-aldehyde (0.3 g), 3-aminopyrazole (0.17 g) and 1-(1-acetylpiperidin-4-yl)-2-cyanoethan-1-one (0.4 g) in acetonitrile (10 mL) was heated under reflux overnight. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration to give the title compound (0.49 g) as yellow crystals.

Workup

  1. extractionAfter acidification with hydrochloric acid, the mixture was extracted with ethyl acetate
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (10:1))

Sources & evidence

ORD record
ord-4ce957c5c44d47dfb464594dcad8e44e
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

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