3-Aminopropionitrile → (S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide

HRID 327613Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 327613
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:16][CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:41][CH2:42][CH2:43][C:44]#[N:45]>C(OCC)(=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[CH:16][CH:15]=1)[C:10]([NH:45][CH2:44][CH2:43][C:42]#[N:41])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 16473-AminopropionitrileHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2761796N-alpha-t-Butyloxycarbonyl-L-biphenylalanine (Boc-L-Bip-OH)

Produkt 1

HCID 53856625(S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

(S)-2-t-Butoxycarbonylamino-3-biphenyl-4-yl-propionic acid (J. Org. Chem., 1992, 57, 379; 20 g, 58 mmol) in ethyl acetate (300 mL) and methylene chloride (75 mL) is cooled under nitrogen to 0° with an ice bath and treated with N-methylmorpholine (6.5 mL, 58 mmol). Isobutyl chloroformate (7.6 mL, 58 mmol) is added dropwise. After 5 minutes of stirring, 3-aminopropionitrile (4.52 g, 64 mmol) in methylene chloride (50 mL) is added over 4 minutes. Stirring is continued for 1 hour at 0° then for 4 hours at room temperature. Ethyl acetate (300 mL) is added and the solution is successively washed with cold water (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL). The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue is triturated with ether (150 mL). The solid is filtered off, washed with cold ether and dried under high vacuum to give (S)-2-t-butoxycarbonylamino-3-biphenyl-4-yl-N-(2-cyanoethyl)-propionamide as a colorless crystalline solid, m.p. 163°-164°; [α]D =+3.58° (c 1, CHCl3).

Aufarbeitung

  1. stirringStirring
  2. waitis continued for 1 hour at 0°
  3. waitfor 4 hours at room temperature
  4. washthe solution is successively washed with cold water (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL)
  5. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is triturated with ether (150 mL)
  9. filtrationThe solid is filtered off
  10. washwashed with cold ether
  11. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-c1765385800a4fab95318ee183e34120
Quelldatensatz
uspto-grants-1993_12
Patentnummer
US05273990

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