65709-33-3

2-(4-Fluorophenyl)piperazine (Item No. 24421) is an analytical reference standard categorized as a piperazine. This product is intended for research and forensic applications.WARNING This product is not for human or veterinary use.

An ethanol (100 mL) solution of ethylenediamine (7.4 g, 123.5 mmol) was added dropwise to a stirred ethanol (300 mL) solution of 4-fluorobenzoylcarboxaldehyde (21.0 g, 123.5 mmol) over 15 minutes, keeping the reaction mixture stirred. The reaction lasted for 4 hours. Sodium borohydride (23.5 g, 622 mmol) was then added and the mixture was stirred at room temperature overnight. Water (200 mL) was added and stirring was continued for 1 hour, after which most of the ethanol was removed under reduced pressure. The concentrated solution was extracted with dichloromethane (4 x 100 mL) and the organic phases were combined, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give a light yellow solid (19.0 g, 86% yield). The solid (8.8 g) was dissolved in methanol (60 mL) and added to a solution of N-acetyl-L-leucine (16.5 g, 95.2 mmol) in methanol (100 mL). Ethyl acetate (550 mL) was added and the mixture was allowed to stand overnight at room temperature. The precipitate was collected by filtration and dried to give a solid (9.0 g). The solid was dissolved in 4 M NaOH aqueous solution (100 mL) and extracted with dichloromethane (4 x 100 mL). The organic phases were combined, washed with brine and the solvent was removed under reduced pressure to give a solid (3.1 g). The solid was recrystallized by ethyl acetate to give the S-enantiomer 2-(4-fluorophenyl)-piperazine (2.23 g). The enantiomeric excess was determined by chiral chromatography under the following conditions: column: Phenomenex Chirex (S)-ICR 250×4.6 mm; mobile phase: n-heptane:ethanol [80:20] + 0.3% TFA; detection wavelength: 254 nm; flow rate: 1 mL/min; UV sensitivity: 0.1 AUF. The sample was analyzed using known chiral compounds and the racemate as reference. racemate as reference, the sample was dissolved in 1 mL of n-heptane:ethanol [75:25] at a concentration of about 1 mg/mL.

[1] Patent: WO2006/86705, 2006, A1. Location in patent: Page/Page column 58