Potassium Hydroxide → alpha-(2-Chlorophenyl)-alpha-[2-[(1-methylethyl) (phenylmethyl)amino]ethyl]-1-piperidine butanenitrile

HRID 1647550

Reaction equation

HRID 1647550 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:11]#[N:12].Cl.Cl[CH2:23][CH2:24][N:25]([CH:33]([CH3:35])[CH3:34])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CS(C)=O.CCCCCCC.O>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]([CH2:23][CH2:24][N:25]([CH:33]([CH3:34])[CH3:35])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:11]#[N:12]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 110435962-(2-Chlorophenyl)-4-(piperidin-1-yl)butanenitrile2×HCID 24185321N-(2-chloroethyl)-N-(1-methylethyl)benzenemethanamine, monohydrochloride

Product 1

HCID 11112943alpha-(2-Chlorophenyl)-alpha-[2-[(1-methylethyl) (phenylmethyl)amino]ethyl]-1-piperidine butanenitrileYield 100.5%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolvent3×HCID 962WaterSolventHCID 8900HeptaneSolvent

Conditions

Temperature
25 °C

Procedure

To a reaction vessel under a nitrogen atmosphere was charged 35.0 kg of pulverized potassium hydroxide (90%) and 34.0 L of dimethyl sulfoxide. A solution of 29.5 kg of α-(2-chlorophenyl)-1-piperidinebutanenitrile (product of Example 3) in 23 L of dimethyl sulfoxide was added while maintaining the temperature below 25° C. A solution of 30.7 kg of N-(2-chloroethyl)-N-(1-methylethyl)benzenemethanamine, monohydrochloride in 112 L of dimethyl sulfoxide was added while maintaining the temperature below 20° C. The mixture was stirred at 25° C. until the reaction was complete as indicated by gas chromatographic analysis (GC Method C). The mixture was cooled and diluted with 122 L of heptane and 200 L of water. The layers were separated, and the organic phase was filtered through a layer of diatomaceous earth. The filter cake was washed with 40 L of heptane. The combined organic phase was washed twice with 70 L of water and dried by azeotropic distillation. The solvent was removed by distillation under reduced pressure to give 49.4 kg (100.0%) of the title product α-(2-chlorophenyl)-α-[2-[(1-methylethyl)(phenylmethyl)amino]ethyl]-1-piperidinebutanenitrile as an oil. Analysis calcd for C27H36ClN3 : C,74.03; H,8.28; Cl,8.09; N,9.59. Found: C,73.35; H,8.36; Cl,7.27; N,9.15. The crude product (oil) was carried forward to the next step without purification. The purity of the title compound was estimated to be >85% based on GC Method C.

Workup

  1. temperaturewhile maintaining the temperature below 25° C
  2. temperaturewhile maintaining the temperature below 20° C
  3. temperatureThe mixture was cooled
  4. customThe layers were separated
  5. filtrationthe organic phase was filtered through a layer of diatomaceous earth
  6. washThe filter cake was washed with 40 L of heptane
  7. washThe combined organic phase was washed twice with 70 L of water
  8. customdried by azeotropic distillation
  9. customThe solvent was removed by distillation under reduced pressure

Sources & evidence

ORD record
ord-22ea6c4e12af4dceb5cabe1e6ca8995d
Source dataset
uspto-grants-1995_07
Patent number
US05432284

Linked notes

Loading…