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

Participants

Reaction Steps

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.

Provenance & Evidence