Ethylene Glycol → Methyl β,β-dimethyl-1-(phenylmethyl)-4-piperidinebutanoate

HRID 1059327Notes

Reaction equation

HRID 1059327 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]([CH3:20])([CH3:19])[CH2:16][C:17]#N)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:21].[K+].Cl.S(Cl)(Cl)=O.C(O)[CH2:29][OH:30]>CO.C(O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]([CH3:20])([CH3:19])[CH2:16][C:17]([O:30][CH3:29])=[O:21])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 24386Thionyl ChlorideHCID 18670287HCID 18670287, compound

Product 1

HCID 18670602Methyl β,β-dimethyl-1-(phenylmethyl)-4-piperidinebutanoate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 4.7 g of 4-(1-benzylpiperidin-4-yl)-3,3-dimethylbutyronitrile in ethylene glycol (20 ml) was added 30 ml of an aqueous solution of 23 g of potassium hydroxide and the resulting mixture was reacted at 200° C. for 10 hours. After bringing back to room temperature, water was added to the reaction mixture. Then the reaction mixture was made weakly acidic with hydrochloric acid. After adding ethanol, the solvent was distilled off under reduced pressure. The crude product thus obtained was suspended in 500 ml of methanol and 6.3 ml of thionyl chloride was dropped thereinto at 0° C. After stirring at room temperature for 72 hours, the solvent was distilled off under reduced pressure. Then an aqueous solution of sodium hydroxide was added to the residue followed by extraction with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 3.5 g of the title compound as a colorless oily substance.

Workup

  1. customthe resulting mixture was reacted at 200° C. for 10 hours
  2. customAfter bringing back to room temperature
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe crude product thus obtained
  5. customat 0° C
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionThen an aqueous solution of sodium hydroxide was added to the residue
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe extract was washed with a saturated aqueous solution of sodium chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationAfter distilling off the solvent under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2cdadcda8c194f36a45da7f21f18fd4b
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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