TFA-Protected α-Amino Acid N-Hydroxysuccinimide Ester: Application for Inter- and Intramolecular Acylation

The TFA-α-amino acid was prepared with reported procedure 1,2 with slightly modification.Triethylamine (33 mmol, 1.5 equiv.) was added to a solution of α-amino acid (22 mmol) in MeOH (22 mL).After 5 min, ethyl trifluoroacetate (29 mmol, 1.3 equiv.) was added and the reaction was allowed to stir for 24 h.The solvent was removed by rotary evaporation and the residue that remained was dissolved in H 2 O and acidified with concentrated HCl.The mixture was extracted with ethyl acetate for several times and the organic layers were combined and washed with brine, dried by MgSO 4 , filtered, and concentrated by rotary evaporation.Further subjection into high vacuum for overnight, if needed to solidify the product (TFA-L-/D-Phe, L-/D-2 and TFA-L-/D-Pro, L-/D-20).(S)-3-phenyl-2-(2,2,2-trifluoroacetamido)propanoic acid (TFA-L-Phe, L-2).Colorless amorphous mass.[α] D = +13 (c 1.0, MeOH); Lit. 3 [α] D = +17.2(c 2, Ethanol).IR (neat) ν : 3319, 3099, 3033, 2929, 1739, 1706 cm -1 . 1 H-NMR (270 MHz, CDCl 3 ) δ: 7.38-7.30(3H, m, Ar-H), 7.14 (2H, d, J = 7.6 Hz, Ar-H), 6.72 (1H, br s, NH), 4.94 (1H, dt, J = 7.6, 5.6 Hz, CHNH), 3.31 (1H, dd, J = 14.2, 5.6 Hz, CH 2 CH), 3.22 (1H, dd, J = 14.2, 5.6 Hz, CH 2 CH) ppm. 13C-NMR (67.5 MHz, CDCl 3 ) δ: 174.2, 156.7 (q, 2 J CF = 38.2Hz), 134.2, 129.2 (2 x CH), 129.0 (2 x CH), 127.8, 115.5 (q, 1 J CF = 287.2Hz), 53.2, 36.9 ppm.HRMS-ESI (m/z) [M + H] + calcd for C 11 H 11 F 3 NO 3 262.0691,found 262.0699.(R)-3-phenyl-2-(2,2,2-trifluoroacetamido)propanoic acid (TFA-D-Phe, D-2).Colorless amorphous mass.[α] D = -13 (c 1.0, MeOH); Lit. 4 [α] D = -17.2(c 2, Ethanol).IR (neat) ν : 3320,