3-Chloro-4-fluoroaniline → 3-Chloro-4-fluorophenylpiperazine

Participants

Reaction Steps

A xylene (20 ml.) solution of 3-chloro-4-fluoroaniline (5.0 g., 34.3 mmol) and bis-(2-chloroethyl)amine hydrochloride (6.13 g., 34.3 mmol) is heated to reflux for 64 hrs. The mixture is extracted with warm water and the aqueous phase then extracted with methylene chloride. The aqueous phase is made basic with 50% sodium hydroxide and extracted with methylene chloride which is dried over potassium carbonate and concentrated under reduced pressure. Residual material is distilled and the fraction having a b.p. of about 100° C. at 0.25 mmHg collected. Conversion of the amine to the hydrochloride salt and crystallization from ethanol affords N-(3-chloro-4-fluorophenyl)piperazine.

Provenance & Evidence