Hydrochloric Acid → HCID 86681592, Verbindung

Temperatur

25 °C

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.

1. temperaturewhile maintaining the temperature at 20-25° C
2. customThe cooling bath was removed
3. additionThe reaction mixture was added to ice (500 mL)
4. temperaturewhile maintaining the quench temperature at 15-20° C
5. filtrationThe white solid was filtered off
6. washwashed with ice-cold H2O
7. dissolutionThe residue was dissolved in a 1:1 mixture of H2O/dioxane (100 mL)
8. additionthe pH was adjusted to pH 9 by addition of Na2CO3
9. stirringthe mixture was stirred for 4 hours
10. extractionthe mixture was extracted twice with EtOAc
11. extractionThe combined organic layers were extracted with brine
12. dry with materialdried (MgSO4)
13. concentrationconcentrated under reduced pressure
14. customThe resulting crude product was purified by column chromatography (25%->60% EtOAc/PE)

ORD-Eintrag

ord-425f72a170eb4bb0a448a7569957ecdb

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08609610B2