Reaktionsgleichung
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]=[N+]=[N-])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1.CCO.[Pd]>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([NH2:22])[CH:17]=2)([CH2:14][F:15])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]Komponenten
Edukt 1
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 3
Versuchsvorschrift
A solution of 740 mg (2.118 mmol) [5-(3-azido-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]carbamic acid tert-butyl ester (Example 31h) in 5 ml THF and 5 ml EtOH was stirred in the presence of 35 mg 10% Pd—C under hydrogen. After 3 h the mixture was filtered over celite, concentrated and crystallized from EtOAc/hexane to give a beige solid. The racemic product was separated via prep HPLC on Chiralpak AD-H 250×4.6 mm column using heptan/EtOH 1:1 as an eluent. The desired compound was the slower eluting (R)-enantiomer. TLC: Rf (Hexane/EtOAc 2:1)=0.15. HPLC: RtH4=1.764 min; ESIMS [M+H]+=324.11 1H-NMR (CDCl3, 360 MHz, broad signals due to hindered rotation): 10.5 (br, 1H), 7.12 (br, 1H), 6.69 (d, 1H), 6.59 (br d, 1H), 4.8-4.0 (m, 8H), 1.48 (br s, 9H).
Aufarbeitung
- filtrationAfter 3 h the mixture was filtered over celite,
- concentrationconcentrated
- customcrystallized from EtOAc/hexane
- customto give a beige solid
- customThe racemic product was separated via prep HPLC on Chiralpak AD-H 250×4.6 mm column
- washslower eluting (R)-enantiomer
- customRtH4=1.764 min
Quellen und Nachweise
- ORD-Eintrag
- ord-f7df5f9fb0d046539a2b94723c680f9e
- Quelldatensatz
- uspto-grants-2012_06
- Patentnummer
- US08207164B2
Verknüpfte Notizen
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