N-(2-Aminoethyl)-N-benzylglycine Bis(trifluoroacetate)

• N-(2-Aminoethyl)-N-benzylglycine Bis(trifluoroacetate) [A3419]
• 4-Fluorobenzaldehyde [F0191]
• [Ir(ppy)₂(dtbbpy)]PF₆ [D4887]
• Potassium Hydroxide (Pellets) [P2849]
• Acetonitrile
• Methanol

An oven-dried Schlenck tube was charged with N-(2-aminoethyl)-N-benzylglycine bis(trifluoroacetate) (88 mg, 0.20 mmol), and the system was degassed through N₂ purging (3 x 5 min). 1 mol/L KOH solution in methanol (0.82 mL, 0.82 mmol) and 4-fluorobenzaldehyde (35 mg, 0.28 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 0.5 h. A solution of [Ir(ppy)₂(dtbbpy)]PF₆ (1.8 mg, 2.0 x 10^-3 mmol) in dry acetonitrile (3.2 mL) was added. The reaction was degassed with N₂ bubbling before starting the irradiation and was stirred at room temperature under the exposure of blue LEDs for 3 h. The solution was filtered to remove the trifluoroacetate salt formed. The resulting mixture was concentrated under vacuum and purified with column chromatography (1 : 99 methanol / ethyl acetate on SiO₂), giving 1-benzyl-3-(4-fluorophenyl)piperazine as a yellow oil (43 mg, 80%).

The reaction mixture was monitored by TLC (ethyl acetate, Rf = 0.25) and LCMS.

¹H NMR (400 MHz, CDCl₃); δ 7.35–7.20 (m, 7H), 6.99–6.91 (m, 2H), 4.29 (br, 1H) 3.94 (dd, 1H, J = 10.4, 2.8 Hz), 3.55 (s, 2H), 3.06–2.98 (m, 2H), 2.89–2.82 (m, 2H), 2.27 (ddd, 1H, 11.2, 9.2, 4.8 Hz), 2.20 (m, 1H).

¹³C NMR (101 MHz, CDCl₃); δ 163.8, 161.3, 137.4, 135.7, 129.2, 128.4, 127.5, 115.5, 63.0, 59.5, 51.9, 45.5.

• Visible-Light-Driven CarboxyLic Amine Protocol (CLAP) for the Synthesis of 2-Substituted Piperazines under Batch and Flow Conditions
  • R. Gueret, L. Pelinski, T. Bousquet, M. Sauthier, V. Ferey, A. Bigot, Org. Lett. 2020, 22, 5157.