Potassium Hydroxide → HCID 22613843, compound

HRID 844550Notes

Reaction equation

HRID 844550 reaction equation
[OH-].[K+].C([CH:5]([C:11]1([C:24]2[CH:29]=[C:28]([CH3:30])[CH:27]=[C:26]([CH3:31])[CH:25]=2)[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:13][CH2:12]1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])#N>O.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:17]([N:14]1[CH2:13][CH2:12][C:11]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])([C:24]2[CH:25]=[C:26]([CH3:31])[CH:27]=[C:28]([CH3:30])[CH:29]=2)[CH2:16][CH2:15]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 22613825HCID 22613825, compound

Product 1

HCID 22613843HCID 22613843, compoundYield 45.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of potassium hydroxide (3.4 g) in water (20 ml) was added to a solution of ethyl 2-cyano-2-(1-benzyl-4-(3,5-dimethylphenyl)piperidin-4-yl)ethanoate (4.7 g) (see Preparation 8) in ethanol (24 ml) and the mixture microwaved at 345 kPa (100 psi)/100% power for 2.5 hours. The solvent was removed under reduced pressure and the residue azeotroped with toluene to remove any residual water. The residue was dissolved in ethanol (100 ml), cooled in an ice-bath and the solution saturated with hydrogen chloride gas. The mixture was left to stand at room temperature overnight before re-saturating the solution with hydrogen chloride gas and leaving to stand for a further 24 hours. The solution was filtered and the solvent removed from the filtrate under reduced pressure to give a residue which was dissolved in saturated aqueous sodium carbonate solution and extracted twice with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulphate and the solvent removed under reduced pressure to give a residue which was chromatographed on silica gel eluting with a solvent gradient of 97:3 changing to 90:10, by volume, dichloromethane:methanol to give the title compound (2.0 g) as an oil.

Workup

  1. customthe mixture microwaved at 345 kPa (100 psi)/100% power for 2.5 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue azeotroped with toluene
  4. customto remove any residual water
  5. dissolutionThe residue was dissolved in ethanol (100 ml)
  6. temperaturecooled in an ice-bath
  7. waitThe mixture was left
  8. concentrationbefore re-saturating the solution with hydrogen chloride gas
  9. customleaving
  10. waitto stand for a further 24 hours
  11. filtrationThe solution was filtered
  12. customthe solvent removed from the filtrate under reduced pressure
  13. customto give a residue which
  14. extractionextracted twice with dichloromethane
  15. dry with materialdried over anhydrous sodium sulphate
  16. customthe solvent removed under reduced pressure
  17. customto give a residue which
  18. customwas chromatographed on silica gel eluting with a solvent gradient of 97:3 changing to 90:10, by volume, dichloromethane

Sources & evidence

ORD record
ord-0670431219364c6fbd55b42994db2499
Source dataset
uspto-grants-2002_04
Patent number
US06380396B1

Reaction notes

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