Ammonium Chloride → (3R,5S)-1-Benzyl-3,5-dimethylpiperidin-4-one

HRID 1992663Notes

Reaction equation

HRID 1992663 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]([CH3:14])[C:11](=[O:15])[CH:10]([CH3:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O-].[Na+].[Cl-].[NH4+]>CO>[CH2:1]([N:8]1[CH2:13][C@H:12]([CH3:14])[C:11](=[O:15])[C@H:10]([CH3:16])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 222789201-Benzyl-3,5-dimethylpiperidin-4-one

Product 1

HCID 59130974(3R,5S)-1-Benzyl-3,5-dimethylpiperidin-4-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude cis:trans mixture of 1-benzyl-3,5-dimethylpiperidin-4-one (typically 6:1 cis:trans) (45 g) was added to a 5% solution of sodium methoxide in methanol (500 mL) and stirred at room temperature for 6 hours. Saturated aqueous ammonium chloride (30 mL) was added and the mixture stirred for a further 30 minutes at room temperature. The mixture was evaporated to dryness and then redissolved in dichloromethane (500 mL). The insoluble solids were filtered off and the solvent was then evaporated to give an enriched mixture 96:4 cis:trans by 1H NMR (quantitative mass recovery). Longer reaction times did not give any further enrichment. If required, pure cis-product could then be obtained by chromatographic purification as described above.

Workup

  1. stirringthe mixture stirred for a further 30 minutes at room temperature
  2. customThe mixture was evaporated to dryness
  3. dissolutionredissolved in dichloromethane (500 mL)
  4. filtrationThe insoluble solids were filtered off
  5. customthe solvent was then evaporated
  6. customto give an enriched mixture 96:4 cis
  7. customLonger reaction times
  8. customdid not give any further enrichment
  9. custompure cis-product could then be obtained by chromatographic purification

Sources & evidence

ORD record
ord-6ca1c5074e2149679978882219271ee9
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

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