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

HRID 989052Notes

Reaction equation

HRID 989052 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-4169cda195e34f58ae3781e1e53aa599
Source dataset
uspto-grants-2003_10
Patent number
US06638942B1

Reaction notes

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