Benzene → 3,4,4-Trimethoxy-1-(phenylmethyl)piperidine ethanedioate

HRID 345547Notes

Reaction equation

HRID 345547 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].[OH-].[Na+].[CH:21]1C=CC=CC=1.S(OC)(OC)(=O)=[O:28]>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.O>[C:4]([OH:28])(=[O:16])[C:3]([OH:17])=[O:2].[CH3:21][O:16][CH:4]1[C:3]([O:17][CH3:18])([O:2][CH3:1])[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:5]1

Participants

7

Reactant 4

HCID 241BenzeneHCID 6497Dimethyl Sulfate2×HCID 14798Sodium HydroxideHCID 30192741-Benzyl-4,4-dimethoxypiperidin-3-ol

Product 1

HCID 867442673,4,4-Trimethoxy-1-(phenylmethyl)piperidine ethanedioate

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent

Procedure

To a stirred mixture of 85 parts of 4,4-dimethoxy-1-(phenylmethyl)-3-piperidinol and 480 parts of sodium hydroxide solution 60% were added 288 parts of benzene and 0.5 parts of N,N,N-triethylbenzenemethanaminium chloride. Then there were added dropwise 49.2 parts of dimethyl sulfate at a temperature below 30° C. After stirring overnight at room temperature, there was added another portion of 13.3 parts of dimethyl sulfate and stirring was continued for 4 hours at room temperature. The reaction mixture was cooled, 640 parts of water were added and the layers were separated. The aqueous phase was extracted with benzene. The formed suspension was filterd and the filter-cake was set aside. The combined organic phases were washed with water, dried, filtered and evaporated. The oily residue was distilled (bp. 138° C. at 1 mm. pressure). The distillate was converted into the ethanedioate salt in 2propanol. The salt was filtered off and crystallized from ethanol, yielding 34.9 parts of 3,4,4-trimethoxy-1-(phenylmethyl)piperidine ethanedioate; mp. 180.6° C. (intermediate 58).

Workup

  1. stirringstirring
  2. waitwas continued for 4 hours at room temperature
  3. temperatureThe reaction mixture was cooled
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with benzene
  6. washThe combined organic phases were washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. distillationThe oily residue was distilled (bp. 138° C. at 1 mm. pressure)
  11. filtrationThe salt was filtered off
  12. customcrystallized from ethanol

Sources & evidence

ORD record
ord-794fbd96fb8444f78871bcd72262bca0
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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