Water → 4-(3-Chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine

HRID 635900Notes

Reaction equation

HRID 635900 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][C:9]#[N:10])=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Cl[CH2:14][CH2:15][N:16]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=1)[CH2:17][CH2:18]Cl.O>CS(C)=O>[Cl:1][C:2]1[C:3]([C:8]2([C:9]#[N:10])[CH2:18][CH2:17][N:16]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=3)[CH2:15][CH2:14]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 415290Bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amineHCID 180050122-(3-Chloropyridin-2-yl)acetonitrile

Product 1

HCID 180049074-(3-Chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidineYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A solution of 3-chloro-2-pyridylacetonitrile [prepared by the method described in JP08295663] (1.46 g, 9.57 mmol) in DMSO (19 mL) was slowly added to NaH (60% oil dispersion, 1.01 g, 25.3 mmol), and the mixture was stirred at room temperature for 1 h. A solution of N,N-bis(2-chloroethyl)-p-methoxybenzylamine (2.21 g, 8.43 mmol) in DMSO (19 ml,) was added, and the resulting mixture was stirred at 75° C. for 4 h. After cooling, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2) to give 4-(3-chloro-2-pyridyl)-4-cyano-1-(4-methoxyphenyl)methylpiperidine 1 (1.91 g, 60%) as an orange oil.

Workup

  1. stirringthe resulting mixture was stirred at 75° C. for 4 h
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2)

Sources & evidence

ORD record
ord-cc03fe66e7c9479ea8483b9322076b8b
Source dataset
uspto-grants-2001_02
Patent number
US06191160B1

Reaction notes

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