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Benzyl Bromide → (S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate

HRID 80364
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 80364
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:20][C:21]#[CH:22])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[N-:36]=[N+:37]=[N-:38].[Na+].[CH:40]1[CH:45]=[CH:44][C:43]([CH2:46]Br)=[CH:42][CH:41]=1>CN(C=O)C.O.O.CCOC(C)=O>[CH2:46]([N:36]1[CH:22]=[C:21]([CH2:20][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[N:38]=[N:37]1)[C:43]1[CH:44]=[CH:45][CH:40]=[CH:41][CH:42]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 7498Benzyl BromideHCID 33557Sodium Azide2×HCID 23667548Sodium AscorbateHCID 57326824(S)-benzyl 2-(tert-butoxycarbonylamino)pent-4-ynoate

Produkt 1

HCID 59166425(S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel
HCID 8857Ethyl AcetateLösungsmittel
HCID 21962138N,N-Dimethylformamide--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

To a mixture of (S)-benzyl 2-(tert-butoxycarbonylamino)pent-4-ynoate (0.50 g, 1.65 mmol), sodium ascorbate (0.036 g, 0.18 mmol), CuSO4.5H2O (0.022 g, 0.09 mmol) and NaN3 (0.13 g, 2.1 mmol) in DMF-H2O (5 mL, 4:1) at rt was added BnBr (0.24 mL, 2.02 mmol) and the mixture was warmed to 65° C. After 5 h LCMS indicated low conversion. A further portion of NaN3 (100 mg) was added and heating was continued for 12 h. The reaction was poured into EtOAc and H2O and shaken. The layers were separated and the aqueous layer extracted 3× with EtOAc and the combined organic phases washed (H2O x3, brine), dried (Na2SO4), filtered, and concentrated. The residue was purified by flash (Biotage, 40+M 0-5% MeOH in CH2Cl2; TLC 3% MeOH in CH2Cl2) to afford a light yellow oil which solidified on standing (748.3 mg, 104%). The NMR was consistent with the desired product but suggests the presence of DMF. The material was used as is without further purification. 1HNMR (400 MHz, DMSO-d6) δ 7.84 (s, 1H), 7.27-7.32 (m, 10H), 5.54 (s, 2H), 5.07 (s, 2H), 4.25 (m, 1H), 3.16 (dd, J=1.0, 5.3 Hz, 1H), 3.06 (dd, J=5.3, 14.7 Hz), 2.96 (dd, J=9.1, 14.7 Hz, 1H), 1.31 (s, 9H).

Aufarbeitung

  1. temperatureheating
  2. waitwas continued for 12 h
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted 3× with EtOAc
  5. washthe combined organic phases washed (H2O x3, brine)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash (Biotage, 40+M 0-5% MeOH in CH2Cl2; TLC 3% MeOH in CH2Cl2)
  10. customto afford a light yellow oil which

Quellen und Nachweise

ORD-Eintrag
ord-26183392d328439ab77c2b2c2e92cdd4
Quelldatensatz
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08846023B2

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