Citric Acid → benzyl (2S)-2-(4,4,4-trifluorobutanoylamino)propanoate

Participants

Reaction Steps

Add successively L-alanine benzyl ester hydrochloride (7.00 g, 32.5 mmol), diisopropylethylamine (28.30 mL, 162.3 mmol), 1-hydroxybenzotriazole hydrate (7.46 g, 48.7 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (9.33 g 48.7 mmol) to a solution of 4,4,4-trifluorobutyric acid (7.131 g, 48.7 mmol) in dichloromethane (162 mL) at ambient temperature under nitrogen and stir for 20 hours. Add a 20% aqueous solution of citric acid (150 mL, 162 mmol), stir mixture for 5 minutes and separate layers. Extract from aqueous with dichloromethane (100 mL). Wash combined organics with saturated aqueous solution of sodium bicarbonate (150 mL), dry over magnesium sulfate and concentrate. Purify the residue by flash chromatography, eluting with hexane:ethyl acetate (4:1 to 2:1) to give the title compound as a white solid (9.22 g, 30.4 mmol, 94%). MS (m/z): 304 (M+1); [α]N825=−44.6° (c=5.0, methanol).

Provenance & Evidence