1,2-Dichloroethane → (S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyric acid benzyl ester

HRID 1477155Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1477155
[C:1]([O:5][C:6]([N:8]([CH3:14])[C@@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[NH2:30][C@@H:31]([CH:42]([CH3:44])[CH3:43])[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33].CN1CCOCC1>C(Cl)Cl>[CH2:35]([O:34][C:32](=[O:33])[C@@H:31]([NH:30][C:10](=[O:12])[C@@H:9]([N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:14])[CH3:13])[CH:42]([CH3:44])[CH3:43])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 11601206L-Valine benzyl ester hydrochloride

Produkt 1

HCID 117871378(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyric acid benzyl esterAusbeute 89,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)propanoic acid (4.06 g, 20.0 mmol, Eq: 1), HOAT (4.08 g, 30.0 mmol, Eq: 1.5) and EDC (5.74 g, 30.0 mmol, Eq: 1.5) in DCM (200 mL), was added a solution of (S)-benzyl 2-amino-3-methylbutanoate hydrochloride (5.35 g, 22.0 mmol, Eq: 1.1) and N-methylmorpholine (4.45 g, 4.83 mL, 43.9 mmol, Eq: 2.2) in 50 mL of DCM. The reaction mixture was stirred at 23° C. for 3 h. The clear yellow solution was concentrated in vacuo. The residue was taken up in EtOAc and washed with saturated aqueous NaHCO3 (1×300 mL), 5% aqueous KHSO4 and brine (1×300 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 0% to 80% EtOAc in hexanes) to afford (S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyric acid benzyl ester as a colorless oil (7.02 g), m/z=393 (M+H).

Aufarbeitung

  1. concentrationThe clear yellow solution was concentrated in vacuo
  2. washwashed with saturated aqueous NaHCO3 (1×300 mL), 5% aqueous KHSO4 and brine (1×300 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 0% to 80% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4e07e0eab42449989a9dd4e0a48822c7
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403768B2

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