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

HRID 28160Notes

Reaction equation

HRID 28160 reaction equation
[C:1]1([NH:7][C:8]2([CH2:21][OH:22])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=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:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=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-(phenylamino)-1-(phenylmethyl)-4-piperidinemethanol in 90 parts of benzene are added 0.2 parts of N,N,N-triethylbenzenemethanaminium chloride and 150 parts of a 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 temerature, first for 2 h.30 and further, after the addition of a second portion of 2.6 parts of dimethyl sulfate, for 1 h.30. The reaction mixture is cooled in ice-water 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 24.8 parts of 4-(methoxymethyl)-N-phenyl-1-(phenylmethyl)-4-piperidinamine as a residue.

Workup

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

Sources & evidence

ORD record
ord-5881ff5f27e0451eb0bef9e28edc1c20
Source dataset
uspto-grants-1980_09
Patent number
US04225606

Reaction notes

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