At room temperature, γ-aminobutyric acid (2.00 g, 19.4 mmol) was dissolved in 14 mL of 10% NaHCO3 aqueous solution. Subsequently, a solution of 9-fluorenylmethyl-N-succinimidyl carbonate (4 g, 11.7 mmol) in acetonitrile (40 mL) was slowly added dropwise over a period of 2 hours. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature for 1 hour. After completion of the reaction, the acetonitrile was removed by distillation under reduced pressure. The aqueous phase was acidified to pH 1 with 10% HCl, at which time a white precipitate was produced. The precipitate was washed sequentially with two portions of 20 mL of water and 20 mL of ethyl acetate, and then dried under reduced pressure to give 4-(fluorenylmethoxycarbonylamino)butanoic acid (Fmoc-GABA) as a white solid in 73% (2.8 g) yield. The structure of the product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR, DMSO-d6, 400 MHz), nuclear magnetic resonance carbon spectroscopy (13C NMR, DMSO-d6, 100 MHz) and mass spectrometry (ESI+).1H NMR (DMSO-d6, 400 MHz): δ 7.89 (d, 2H, J = 7.4 Hz), 7.44 (d, 2H, J = 7.2 Hz), 7.42 (t, 2H, J = 7.5 Hz), 7.35 (s, 1H), 7.33 (t, 2H, J = 7.0 Hz), 4.30 (d, 2H, J = 7 Hz), 4.21 (t, 1H, J = 6.7 Hz), 3.01 (q, 2H, J = 5.6 Hz), 2.20 (t, 2H, J = 7.3 Hz ), 1.63 (q, 2H, J = 7.1 Hz); 13C NMR (DMSO-d6, 100 MHz): δ 142.6, 139.4, 137.4, 128.9, 127.2, 124.2, 121.3, 120.0, 109.6, 77.5, 61.8, 51.1, 31.6; MS (ESI+): m/ z (intensity), 325.8 ([M + H]+, 100%).
