Iodine → [1-(4-Benzyloxy-3-methoxy-phenyl)-2-(3-ethoxy-phenyl)-ethyl]-(2,2-dimethoxy-ethyl)-amine

HRID 1833187Notes

Reaction equation

HRID 1833187 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7]Cl)[CH3:2].[Mg].II.[CH2:15]([O:22][C:23]1[CH:36]=[CH:35][C:26]([CH:27]=[N:28][CH2:29][CH:30]([O:33][CH3:34])[O:31][CH3:32])=[CH:25][C:24]=1[O:37][CH3:38])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Cl-].[NH4+]>C(OCC)C.O>[CH2:15]([O:22][C:23]1[CH:36]=[CH:35][C:26]([CH:27]([NH:28][CH2:29][CH:30]([O:31][CH3:32])[O:33][CH3:34])[CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=2)=[CH:25][C:24]=1[O:37][CH3:38])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 5462224Magnesium2×HCID 22048289(4-Benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amineHCID 220483721-(Chloromethyl)-3-ethoxybenzene

Product 1

HCID 22048411[1-(4-Benzyloxy-3-methoxy-phenyl)-2-(3-ethoxy-phenyl)-ethyl]-(2,2-dimethoxy-ethyl)-amine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

3-Ethoxybenzylchloride (13.6 g, 80 mmol) was dissolved in diethyl ether (100 mL) and magnesium metal (2.04 g, 84 mmol) was added without stirring. Several crystals of iodine were added to the magnesium “pile”. When the reaction begins, stirring is started and external cooling is applied as necessary to maintain gentle refluxing. Once the initial reaction was complete, the mixture was refluxed for 1 h to complete the reaction. The resulting gray/green mixture was cooled in an ice-bath and (4-benzyloxy-3-methoxy-benzylidene)-(2,2-dimethoxy-ethyl)-amine (13.2 g, 40 mmol) in diethyl ether (60 mL) was added dropwise (a precipitate forms with each drop). After addition was complete, the resulting suspension was heated at reflux for 2 hours. The mixture was cooled in an ice-bath and saturated aqueous ammonium chloride solution (100 mL) was carefully added dropwise. The mixture was stirred at 0° C. for 15 minutes and then room temperature for 1 h. Water (80 mL) was added, and the mixture was filtered. The organic layer was separated, washed with water (50 mL), saturated aqueous sodium chloride solution (40 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to afford [1-(4-benzyloxy-3-methoxy-phenyl)-2-(3-ethoxy-phenyl)-ethyl]-(2,2-dimethoxy-ethyl)-amine as a light tan solid which was used without further purification.

Workup

  1. stirringstirring
  2. temperatureexternal cooling
  3. temperatureto maintain gentle refluxing
  4. customOnce the initial reaction
  5. temperaturethe mixture was refluxed for 1 h
  6. customthe reaction
  7. temperatureThe resulting gray/green mixture was cooled in an ice-bath
  8. additionAfter addition
  9. temperaturethe resulting suspension was heated
  10. temperatureat reflux for 2 hours
  11. temperatureThe mixture was cooled in an ice-bath
  12. stirringThe mixture was stirred at 0° C. for 15 minutes
  13. filtrationthe mixture was filtered
  14. customThe organic layer was separated
  15. washwashed with water (50 mL), saturated aqueous sodium chloride solution (40 mL)
  16. dry with materialdried over magnesium sulfate
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8696af162b5343ca8678b410e482f42b
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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