Benzene → 1-Benzyl-4-(methoxymethyl)-N-phenylpiperidin-4-amine

HRID 1973799Notes

Reaction equation

HRID 1973799 reaction equation
[NH:1]([C:8]1([CH2:21][OH:22])[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]1C=CC=CC=1.[OH-].[Na+].S(OC)(OC)(=O)=O>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.O>[CH3:23][O:22][CH2:21][C:8]1([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 241BenzeneHCID 6497Dimethyl Sulfate2×HCID 14798Sodium HydroxideHCID 30172301-Benzyl-4-(phenylamino)piperidine-4-methanol

Product 1

HCID 30477241-Benzyl-4-(methoxymethyl)-N-phenylpiperidin-4-amine

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent

Procedure

To a solution of 32 parts of 4-anilino-1-benzyl-4-piperidinemethanol in 90 parts of benzene are added 0.2 parts of N,N,N-triethylbenzenemethanaminium chloride and 150 parts of sodium hydroxide solution 60%. After stirring vigourously, there are added dropwise 10.9 parts of dimethyl sulfate at a temperature below 30° C. Upon completion, stirring is continued at room temperature, first for 2h.30 and further, after the addition of a second portion of 2.6 parts of dimethyl sulfate, for 1h.30. The reaction mixture is cooled in icewater and 200 parts of water are added. The organic phase is separated and the aqueous phase is extracted with benzene. The combined organic phases are washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 3% of methanol, saturated with ammonia, as eluent. The pure fractions are collected and the eluent is evaporated, yielding 4-(methoxymethyl)-N-phenyl-1-(phenylmethyl)-4-piperidinamine as a residue.

Workup

  1. stirringUpon completion, stirring
  2. customis continued at room temperature, first for 2h.30
  3. additionare added
  4. customThe organic phase is separated
  5. extractionthe aqueous phase is extracted with benzene
  6. washThe combined organic phases are washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is purified by column-chromatography over silica gel using
  11. additiona mixture of trichloromethane and 3% of methanol
  12. customThe pure fractions are collected
  13. customthe eluent is evaporated

Sources & evidence

ORD record
ord-81630dfb3b1a4b15838e02c679763eaa
Source dataset
uspto-grants-1976_12
Patent number
US03998834

Reaction notes

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