Iodine → 4-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

HRID 563332Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 563332
[Si:1]([O:8][C@H:9]([CH3:37])[C@@H:10]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([Cl:35])[C:28]=1[CH3:36])[C:11]([NH:13][NH:14][C:15](=[O:25])[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=1)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.II.CCN(CC)CC>C(Cl)Cl>[Si:1]([O:8][C@H:9]([CH3:37])[C@@H:10]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29]([Cl:35])[C:28]=1[CH3:36])[C:11]1[O:25][C:15]([C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)=[N:14][N:13]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 807IodineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 59193039N'-((2R,3R)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazide

Produkt 1

HCID 591930514-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrileAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of N′-((2R,3R)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-4-nitrobenzohydrazide (8.5 g, 15.57 mmol) in CH2Cl2 (250 mL) was added to a pre-cooled (0° C.) mixture of PPh3 (8.17 g, 31.13 mmol), iodine (7.90 g, 31.13 mmol) and Et3N (1.11 mL, 7.94 mmol). The reaction mixture was warmed to room temperature, stirred for 50 minutes and quenched with sat. aq. sodium thiosulfate (400 mL). The solution was extracted with CH2Cl2 (250 mL). The organic extract was washed with sat. aq. sodium thiosulfate (300 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a brown oil, which was purified by flash chromatography over silica gel (20-40% EtOAc in hexanes) to provide the title compound as a light yellow solid (5.5 g, 67%): 1H NMR (400 MHz, CDCl3, δ in ppm) 8.37 (dm, J=9.0 Hz, 2H), 8.18 (dm, J=9.0 Hz, 2H), 7.36 (d, J=8.6 Hz, 1H), 6.61 (d, J=8.6 Hz, 1H), 5.11 (d, J=9.2 Hz, 1H), 4.87 (dd, J=3.9, 8.8 Hz, 1H), 4.46 (dq, J=3.7, 6.3 Hz, 1H), 2.34 (s, 3H), 1.31 (d, J=6.3 Hz, 3H), 0.93 (s, 9H), 0.15 (s, 3H), 0.12 (s, 3H).

Aufarbeitung

  1. temperaturea pre-cooled
  2. customquenched with sat. aq. sodium thiosulfate (400 mL)
  3. extractionThe solution was extracted with CH2Cl2 (250 mL)
  4. extractionThe organic extract
  5. washwas washed with sat. aq. sodium thiosulfate (300 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a brown oil, which
  10. customwas purified by flash chromatography over silica gel (20-40% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-1467f8e781304955b9429c603e64397b
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08067448B2

Notizen zur Reaktion

Wird geladen…