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

HRID 1153963Notes

Reaction equation

HRID 1153963 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.Cl[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]Cl>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([N:5]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:6]=[CH:7][C:8]=1[F:9]

Participants

4

Reactant 2

HCID 97083-Chloro-4-fluoroanilineHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 27792633-Chloro-4-fluorophenylpiperazine

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

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.

Workup

  1. temperatureto reflux for 64 hrs
  2. extractionThe mixture is extracted with warm water
  3. extractionthe aqueous phase then extracted with methylene chloride
  4. extractionextracted with methylene chloride which
  5. dry with materialis dried over potassium carbonate
  6. concentrationconcentrated under reduced pressure
  7. distillationResidual material is distilled
  8. customcollected
  9. customConversion of the amine to the hydrochloride salt and crystallization from ethanol

Sources & evidence

ORD record
ord-75f09600332041b5a701c834a8945337
Source dataset
uspto-grants-1984_12
Patent number
US04487773

Reaction notes

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