Dimethylformamide → 4,4-Dimethoxy-3-(phenylmethoxy)-1-(phenylmethyl)piperidine

HRID 345541Notes

Reaction equation

HRID 345541 reaction equation
[CH3:1][O:2][C:3]1([O:17][CH3:18])[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH:4]1[OH:16].CN(C)C=O.[H-].[Na+].Cl[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O>[CH3:1][O:2][C:3]1([O:17][CH3:18])[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:5][CH:4]1[O:16][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 30192741-Benzyl-4,4-dimethoxypiperidin-3-ol

Product 1

HCID 150967524,4-Dimethoxy-3-(phenylmethoxy)-1-(phenylmethyl)piperidineYield 64.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred mixture of 37.8 parts of 4,4-dimethoxy-1-(phenylmethyl)-3-piperidinol and 135 parts of N,N-dimethylformamide were added portionwise 4.8 parts of sodium hydride dispersion 78%. The whole was heated to 60°-70° C. and stirring was continued for 30 minutes at 50° C. After cooling to room temperature, there were added dropwise 18.9 parts of (chloromethyl)benzene (exothermic reaction: temperature roses to 37° C.). Upon completion, stirring was continued for 2 hours at room temperature. The reaction mixture was poured onto 500 parts of water and the product was extracted twice with 1,1'-oxybisethane. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was distilled, yielding 33.1 parts (64.6%) of 4,4-dimethoxy-3-(phenylmethoxy)-1-(phenylmethyl)piperidine; bp. 180°-185° C. at 0.3 mm. pressure (intermediate 43).

Workup

  1. temperatureThe whole was heated to 60°-70° C.
  2. stirringUpon completion, stirring
  3. waitwas continued for 2 hours at room temperature
  4. extractionthe product was extracted twice with 1,1'-oxybisethane
  5. washThe combined extracts were washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column-chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. distillationThe residue was distilled

Sources & evidence

ORD record
ord-d83629555e5d46b696324fa179a9da56
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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