2-Fluoroaniline → 1-(2-Fluorophenyl)piperazine

HRID 875008Notes

Reaction equation

HRID 875008 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl.Cl[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]Cl.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC.CO.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[N:4]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

Participants

7

Reactant 3

HCID 95842-FluoroanilineHCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 705291-(2-Fluorophenyl)piperazineYield 31%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

2-Fluoroaniline (4.0 g, 36.0 mmol) and bis-(2-chloroethyl)-amine hydrochloride (6.4 g, 36.0 mmol) were dissolved in n-butanol (40 mL) and potassium carbonate (12.0 g, 86.8 mmol) was added. The reaction mixture was heated to 100° C. for 16 h, cooled to room temperature, and concentrated under reduced pressure. The crude reaction mixture was diluted with 10% MeOH in CHCl3 and filtered. The clear filtrate was concentrated under reduced pressure to get 1-(2-fluorophenyl)piperazine (2.0 g, yield 31%), which was carried through without further purification. 1H NMR (400 MHz, CDCl3) δ 9.95 (br s, 1H), 7.12-6.95 (m, 4H), 3.43 (br s, 8H). MS (ESI) m/z: Calculated for C10H13FN2: 180.11. found: 180.9 (M+H)+

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe crude reaction mixture
  4. filtrationfiltered
  5. concentrationThe clear filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-e6fa1077ed964255802159f2f303a35e
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

Loading…