Diethylamine → 2-[4-[(Z)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine

HRID 1904565Notes

Reaction equation

HRID 1904565 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=2)=[C:12](\[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)/[CH2:13][CH3:14])=[CH:7][CH:6]=1.[CH2:28]([NH:30][CH2:31]C)C>C(O)C>[CH3:14][CH2:13]/[C:12](/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[C:11](/[C:21]1[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=1)\[C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][N:30]([CH3:31])[CH3:28])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 11092160HCID 11092160, compound

Product 1

HCID 30370062-[4-[(Z)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of E-1-[4-(2-chloroethoxy)phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene (3.05 g) in 33% diethylamine in ethanol (60 ml) was boiled under reflux for 20 hours. The mixture was concentrated, a procedure made necessary only because of escape of the gaseous dimethylamine under these conditions, further 33% dimethylamine solution (60 ml) was added and reflux was continued for a further 20 hours. The mixture was again concentrated and the residue partitioned between ether (50 ml) and aqueous sodium hydroxide (1M; 50 ml). The ether solution was concentrated and the residue applied to a column of silica gel (Merck 15111, 40 g). Column chromatography was need to remove a small amount of unreacted starting material from the product which could not be removed by recrystallisation. This problem and the concentration step during addition of dimethylamine could have been overcome by carrying out the reaction in a sealed bomb. Elution with 5% methylamine in 1:1 ether-light petroleum (b.p. 40°-60° C.) gave 4-iodotamoxifen, which was further purified by recrystallisation from light petroleum (b.p. 40°-60° C.) (2.60 g, 84% yield), identical to that of Example 1.

Workup

  1. temperatureunder reflux for 20 hours
  2. concentrationThe mixture was concentrated
  3. additionwas added
  4. temperaturereflux
  5. concentrationThe mixture was again concentrated
  6. customthe residue partitioned between ether (50 ml) and aqueous sodium hydroxide (1M; 50 ml)
  7. concentrationThe ether solution was concentrated
  8. customto remove a small amount
  9. custombe removed by recrystallisation
  10. concentrationThis problem and the concentration step
  11. additionduring addition of dimethylamine
  12. customthe reaction in a sealed bomb
  13. washElution with 5% methylamine in 1:1 ether-light petroleum (b.p. 40°-60° C.)

Sources & evidence

ORD record
ord-258d1f0f7b68438dbc40955929370854
Source dataset
uspto-grants-1989_06
Patent number
US04839155

Reaction notes

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