Ammonia → Lofexidine

Participants

Reaction Steps

In a variation of the present process, the (-)-2-(2,6-dichlorophenoxy)-propionic acid ethylester obtained as above described, is reacted with an ethanolic solution of ammonia at room temperature and is converted into (+)-2-(2,6-dichlorophenoxy)-propionic acid amide which is difficultly soluble in ethanol. This amide is dehydrated at from 0° to 30° C. with a titanium tetrachloride/tetrahydrofurane complex and 4-methyl-morpholine in chloroform into (-)-2-(2,6-dichlorophenoxy)-propionic acid nitrile. By introducing hydrogen chloride at 0° C., the nitrile is then converted with ethanol in chloroform into (-)-2-(2,6-dichlorophenoxy)-propionimido acid ethylester hydrochloride. This compound is dissolved in ethanol and is cyclized by adding 1,2-diaminoethane to produce (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene. Analogously to the previous process, (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene hydrochloride is produced from the (-)-base thus obtained.

Provenance & Evidence