Acetonitrile → 1-(1-Phenylpiperidin-4-yl)-2-cyanoethan-1-one

HRID 489440Notes

Reaction equation

HRID 489440 reaction equation
[C:1](#[N:3])[CH3:2].[Li]CCCC.[C:9]1([N:15]2[CH2:20][CH2:19][CH:18]([C:21]([O:23]CC)=O)[CH2:17][CH2:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1COCC1>[C:9]1([N:15]2[CH2:16][CH2:17][CH:18]([C:21](=[O:23])[CH2:2][C:1]#[N:3])[CH2:19][CH2:20]2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 6470Ethyl 1-phenylpiperidine-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 222653371-(1-Phenylpiperidin-4-yl)-2-cyanoethan-1-oneYield 23.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl isonipecotate (8.9 g) in CH2Cl2 (500 mL) was added triphenyl bismus (25 g) and Copper(II)acetate (10.3 g) at room temperature, the mixture was stirred overnight. After filteration, the mixture was extracted with CH2Cl2. 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 ethyl 1-phenylpiperidine-4-carboxylate (8.6 g) as colorless crystals. To a solution of acetonitrile (1.9 g) in THF (200 mL) was added n-BuLi (41 mmol) at −78° C. Further, ethyl 1-phenylpiperidine-4-carboxylate (8.6 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-phenylpiperidin-4-yl)-2-cyanoethan-1-one (2.0 g) as colorless crystals. A solution of 2,1,3-benzoxadiazole-4-aldehyde (0.3 g), 3-aminopyrazole (0.2 g) and 1-(1-phenylpiperidin-4-yl)-2-cyanoethan-1-one (0.5 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 (0.6 g) as colorless 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-9abb965cebf34a29a957ab683a5ae2ba
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

Loading…