Hydrochloric Acid → HCID 86681592, compound

Participants

Reaction Conditions

Reaction Steps

L-Phenylalanine (8, 8.26 g, 50.0 mmol) was added in portions to concentrated H2SO4 (35 mL) maintaining the temperature at 25° C. N-(hydroxymethyl)trichloroacetamide (1.05 eq., 52.5 mmol, 10.1 g) was added in portions while maintaining the temperature at 20-25° C. The cooling bath was removed and the light-brown cloudy solution was stirred at room temperature for 1 hour. The reaction mixture was added to ice (500 mL) and the pH was adjusted to pH 5.5 with 8 M aq. NaOH solution while maintaining the quench temperature at 15-20° C. The white solid was filtered off and washed with ice-cold H2O. The residue was dissolved in a 1:1 mixture of H2O/dioxane (100 mL) and the pH was adjusted to pH 9 by addition of Na2CO3. Next, benzyl chloroformate (7.32 mL, 50.0 mmol) was added and the mixture was stirred for 4 hours. Concentrated aq. HCl was added until pH 1 and the mixture was extracted twice with EtOAc. The combined organic layers were extracted with brine, dried (MgSO4) and concentrated under reduced pressure. The resulting crude product was purified by column chromatography (25%->60% EtOAc/PE) and the title compound was obtained as a colourless solid (yield: 8.29 g, 17.5 mmol, 35%). 1H NMR (400 MHz, CDCl3): δ=10.16 (s, 1H), 7.31-7.21 (m, 6H), 7.13 (d, J=7.88 Hz, 2H), 7.09 (d, J=7.97 Hz, 2H), 5.58 (d, J=8.21 Hz, 1H), 5.05-4.97 (m, 2H), 4.60 (dd, J=13.68, 6.42 Hz, 1H), 4.40 (d, J=5.54 Hz, 2H), 3.14 (dd, J=13.57, 4.65 Hz, 1H), 3.01 (dd, J=13.81, 6.53 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ=174.70, 162.06, 155.85, 135.68, 135.31, 135.15, 129.57, 128.31, 128.28, 127.76, 127.57, 92.30, 66.91, 54.41, 44.54, 36.99 ppm.

Provenance & Evidence