Sodium Methoxide → Methyl cis-[3-(4-ethyl-3,5-dimethoxy-phenyl)-1-methyl-piperidin-4-yl]-acetate

HRID 382810Notes

Reaction equation

HRID 382810 reaction equation
[CH2:1]([C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([CH:11]2[CH2:12][N:13]([CH3:22])[CH2:14][CH2:15]/[C:16]/2=[CH:17]\[C:18]([O:20][CH3:21])=[O:19])=[CH:5][C:4]=1[O:23][CH3:24])[CH3:2].[CH3:25][O-:26].[Na+]>CO>[C:18]([O:20][CH2:21][CH3:25])(=[O:19])[CH3:17].[CH3:8][OH:9].[NH4+:13].[OH-:26].[CH2:1]([C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C@H:11]2[C@@H:16]([CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH2:15][CH2:14][N:13]([CH3:22])[CH2:12]2)=[CH:5][C:4]=1[O:23][CH3:24])[CH3:2]

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 86757543methyl (E)-[3-(4-ethyl-3,5-dimethoxy-phenyl)-1-methyl-piperidin-4-ylidene]acetate

Product 2

HCID 21901312Ethyl acetate methanol ammonium hydroxideHCID 69823475Methyl cis-[3-(4-ethyl-3,5-dimethoxy-phenyl)-1-methyl-piperidin-4-yl]-acetateYield 175.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

g 3) A solution of 6.4 g (19.3 mmol) of methyl (E)-[3-(4-ethyl-3,5-dimethoxy-phenyl)-1-methyl-piperidin-4-ylidene]acetate in 100 ml of methanol was treated with 1.08 g (20 mmol) of sodium methylate and the mixture was heated at reflux for 6 hours. The solution was evaporated and the residue was partitioned between 50 ml of methyl acetate and 50 ml of water. The organic phases were dried (MgSO4), filtered and evaporated. The colorless oil was dissolved in 50 ml of methanol, treated with 125 mg of Pd on charcoal and hydrogenated with hydrogen at room temperature for 12 hours. The catalyst was filtered off and the filtrate was evaporated. Chromatography (silica gel, ethyl acetate/methanol/NH4OH 200:10:1) yielded 5.68 g (88%) of methyl cis-[3-(4-ethyl-3,5-dimethoxy-phenyl)-1-methyl-piperidin-4-yl]-acetate as a colorless oil, Rf=0.23 (silica gel, ethyl acetate/methanol/NH4OH 200:10:1).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 6 hours
  3. customThe solution was evaporated
  4. customthe residue was partitioned between 50 ml of methyl acetate and 50 ml of water
  5. dry with materialThe organic phases were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe colorless oil was dissolved in 50 ml of methanol
  9. additiontreated with 125 mg of Pd on charcoal and hydrogenated with hydrogen at room temperature for 12 hours
  10. filtrationThe catalyst was filtered off
  11. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-92ba79cb4b0c4cf089f8245a00ccf4d3
Source dataset
uspto-grants-2001_10
Patent number
US06310208B1

Reaction notes

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