Hydrochloric Acid → Z-FA-FMK

HRID 2225907Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2225907
C[N:2]1[CH2:7][CH2:6][O:5]CC1.Cl[C:9]([O:11][CH2:12][CH:13]([CH3:15])[CH3:14])=[O:10].[CH3:16][C:17]1[CH:18]=[CH:19][C:20](S(O)(=O)=O)=[CH:21][CH:22]=1.[NH2:27][C@H:28]([C:30]([CH2:32][F:33])=[O:31])[CH3:29].Cl.[CH2:35]1[CH2:39]OC[CH2:36]1>CN(C=O)C>[NH:2]([C:9]([O:11][CH2:12][C:13]1[CH:15]=[CH:39][CH:35]=[CH:36][CH:14]=1)=[O:10])[C@H:7]([C:6]([NH:27][C@H:28]([C:30]([CH2:32][F:33])=[O:31])[CH3:29])=[O:5])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 79724-Methylmorpholine2×HCID 8028TetrahydrofuranHCID 62365Isobutyl chloroformateHCID 131717225HCID 131717225, Verbindung

Produkt 1

HCID 5311161Z-FA-FMKAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
-15 °C

Versuchsvorschrift

Z-phenylalanine (2.29 g, 7.65 mmol) was dissolved in THF (35 mL). The solution was cooled to -10° C. (methanol/ice bath). N-methylmorpholine (NMM; 0.84 mL, 7.65 mmol) was added, followed by isobutyl chloroformate (IBCF; 0.991 mL, 7.65 mmol), added over 3 minutes. With stirring, in a separate flask cooled to -15° C., p-TsOH.AlaCH2F (2.11 g, 7.65 mmol) was dissolved in DMF (7 mL). This solution was added to the mixed anhydride. NMM (0.84 mL, 7.65 mmol) was added. The reaction mixture was stirred for 45 minutes at between -10° C. and -5° C. 1M HCl (50 mL) was added. The mixture was extracted with ethyl acetate (2×50 mL). The organic phases were combined, washed with saturated aqueous NaHCO3 (2×50 mL), brine (50 mL), dried over MgSO4, filtered, and evaporated to dryness. The crude solid was precipitated from 7:1 hexane/CH2Cl2 (100 mL). After filtration, the solid was recrystallized from isiporpanol, yielding pure Z-Phe-AlaCH2F (2.13 g, 72% from p-TsOH.AlaCH2F).

Aufarbeitung

  1. additionadded over 3 minutes
  2. stirringThe reaction mixture was stirred for 45 minutes at between -10° C. and -5° C
  3. extractionThe mixture was extracted with ethyl acetate (2×50 mL)
  4. washwashed with saturated aqueous NaHCO3 (2×50 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude solid was precipitated from 7:1 hexane/CH2Cl2 (100 mL)
  9. filtrationAfter filtration
  10. customthe solid was recrystallized from isiporpanol

Quellen und Nachweise

ORD-Eintrag
ord-9aa4d08b88f0425faad0abaf4c9c1a70
Quelldatensatz
uspto-grants-1994_09
Patentnummer
US05344939

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