Sodium Carbonate → Fmoc-Val-Ala-OH

HRID 1057069Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1057069
[NH2:1][C@H:2]([C:6]([NH:8][C@H:9]([C:11]([OH:13])=[O:12])[CH3:10])=[O:7])[CH:3]([CH3:5])[CH3:4].C([O-])([O-])=O.[Na+].[Na+].[C:20](Cl)([O:22][CH2:23][CH:24]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21]>O.O1CCOCC1>[CH:35]1[C:36]2[CH:24]([CH2:23][O:22][C:20]([NH:1][C@@H:2]([CH:3]([CH3:5])[CH3:4])[C:6]([NH:8][C@@H:9]([CH3:10])[C:11]([OH:13])=[O:12])=[O:7])=[O:21])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]=2[CH:32]=[CH:33][CH:34]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 6992638Val-Ala

Produkt 1

HCID 11165770Fmoc-Val-Ala-OHAusbeute 94,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Versuchsvorschrift

H-Val-Ala-OH 11 (1.0 g, 5.313 mmol, 1.0 eq.) and Na2CO3 (1.42 g, 13.282 mmol, 2.5 eq.) were solubilised in distilled H2O (40 mL) and the mixture was cooled to 0° C. before dioxane (40 mL) was added. Partial precipitation of the amino acid salt occurred. A solution of Fmoc-Cl (1.44 g, 5.579 mmol, 1.05 eq.) dissolved in dioxane (40 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0° C. for 2 hours before the ice bath was removed and the stirring maintained for 16 hours. The solvent was evaporated under reduced pressure and the solid remaining dissolved in water (450 mL). The pH was adjusted to 2 with 1N HCl (25 mL) and the aqueous layer was subsequently extracted with EtOAc (3×250 mL). The combined organics were washed with brine (100 mL), dried over MgSO4, filtered and the volatiles removed under reduced pressure to afford pure HO-Ala-Val-Fmoc 12 as a white solid (2.06 g, 94%). LC/MS (2.758 min (ES+)), m/z: 411.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 12.47 (br s, 1H), 8.20 (d, 1H, J=6.7 Hz), 7.89 (d, 2H, J=7.5 Hz), 7.75 (t, 2H, J=6.8 Hz), 7.43-7.38 (m, 3H), 7.34-7.30 (m, 2H), 4.31-4.16 (m, 4H), 3.88 (dd, 1H, J=8.8, 7.2 Hz), 1.98 (m, 1H), 1.26 (d, 3H, J=7.3 Hz), 0.89 (d, 3H, J=6.8 Hz), 0.86 (d, 3H, J=6.8 Hz).

Aufarbeitung

  1. additionwas added
  2. customPartial precipitation of the amino acid salt
  3. additionwas added dropwise
  4. customwas removed
  5. temperaturethe stirring maintained for 16 hours
  6. customThe solvent was evaporated under reduced pressure
  7. dissolutionthe solid remaining dissolved in water (450 mL)
  8. extractionthe aqueous layer was subsequently extracted with EtOAc (3×250 mL)
  9. washThe combined organics were washed with brine (100 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe volatiles removed under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-ba492c13b2634f709236797b05350530
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09399073B2

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