N-(Trifluoroacetyl)glycine

White Solid

N-(trifluoroacetyl)glycine is an N-acylglycine resulting from the formal condensation of the amino group of glycine with the carboxy group of trifluoroacetic acid. It is a N-acylglycine, a secondary carboxamide and a trifluoroacetamide.

General procedure: 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) inMeOH (22 mL). After 5 min, ethyl trifluoroacetate (29 mmol, 1.3 equiv.) was added and thereaction was allowed to stir for 24 h. The solvent was removed by rotary evaporation and theresidue that remained was dissolved in H2O (35 mL) and acidified with concentrated HCl (4 mL).After stirring for 15 min, the mixture was extracted with ethyl acetate and the organic layerswere combined and washed with brine, dried by MgSO4, filtered, and concentrated by rotaryevaporation. Further subjection into high vacuum for overnight, if needed to solidify the product(L-/D-1a–L-/D-2a, 3a, L-/D-4a–L-/D-8a).To a 30 L reactor equipped with a mechanical stirrer, a thermometer, a reflux condenser, an addition funnel, and nitrogeninlet-outlet was charged TFA (2 L), glycine 16 (2.0 kg, 26.6 mol)with stirring while keeping the inner temperature below 0 Cresulting in a suspension. Then to the suspension was added dropwiseTFAA (6.6 kg, 31.4 mol) with stirring while keeping the innertemperature below 70 C. After addition, the reaction mixture waskept at 70 C and stirred for another 2 h until all solid was dissolved.Completion was demonstrated by disappearance of thestarting material by HPLC after 2 h. The mixture was concentratedto dryness under vacuum at 50 C to obtain the crude 17 as a lightyellow solid. The crude material was purified by re-crystallizationfrom EtOAc (6 L) and heptane (12 L) to afford pure 17 (3.7 kg, 81percent)as a white solid: mp 120–121 C. 1H NMR (400 MHz, D2O) d 4.01 (s, 2 H). 13C NMR (101 MHz, D2O) d 40.86, 117.08, 159.37, 171.66;HRMS (ESI) [C4H4F3NO3H]) calcd 170.0065, found 170.0044.Methyl trifluoroacetate (804 μL, 7.99 mmoles) and triethylamine (928 μL, 6.66 mmoles) were added to a suspension of glycine (500 mg, 6.66 mmoles) in methanol (2.5 mL). After the mixture was stirred vigorously for 18 h, 1 N HCl was added dropwise until the a pH of 2 was obtained. The reaction was added to ethyl acetate (30 mL) was washed with 1 N HCl (2 x 10 mL), dried over MgSOTo a stirred suspension of the intermediate compound obtained from step i) (1.30 g, 7.60 mmol) in 15 ml_ of vinyl acetate, Pd(OAc)2 (0, 02 g, 0.08 mmol) and KOH (0.04 g, 0.76 mmol) were added under argon atmosphere. The solution was stirred overnight at room temperature. The mixture was then quenched with water and diethyl ether was added . The aqueous phase was extracted with diethyl ether (2x50 ml_), washed with brine (3x50 ml_), dried over Na2S04, filtered and the solvent was evaporate. The crude reaction was then purified on silica gel using diethyl ether/petroleum ether (40/60) as eluent to afford the desired product as a pale yellow solid (0.37 g, 25%). NMR characterization : ^-NMR (acetone-de 400 MHz) d 9.00 (1H, s, NH), 7.26 (1H, dd Jcis=6.16 Hz, Jtrans= 13.76 Hz CH), 4.93 (1H, Jtrans= 13.76Hz, CH2), 4.68 (1H, d, Jcis=6.16 Hz, CH2), 4.25 (2H, d, J=4.25, CH2) 13C-NMR (acetone-de, 100 MHz) d 166.6 [C, COOVinyl], 158.3 [C, 2JC-F=36.7 Hz, COCF3], 141.8 [CH], 116.9 [C, JC-F=285.2 HZ, COCF3], 99.0 [CHCH2], 41.5 [NHCH2] 19F NMR (acetone-de 376 MHz EK 492) d -76.5A solution of 5 (1 1.0 g, 29.0 mmol), EDCI (1 1.3 g, 59.0 mmol), HOBT (2.0 g, (0352) 59.0 mmol), F3COGIyOH (7.6 g, 44.0 mmol) and triethylamine (1 1.9 g, 1 18.0 mmol) in dichloromethane (200 mL) was stirred at room temperature overnight. The reaction mixture was washed with water to give the crude product. The crude product was purified by silica gel column chromatography to give the desired product (12.0 g, 77%).

Molecular Weight:171.07
XLogP3:0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:2
Exact Mass:171.01432748
Monoisotopic Mass:171.01432748
Topological Polar Surface Area:66.4
Heavy Atom Count:11
Complexity:176
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes