Iodine → tert-butyl(1-(5-((5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)cyclopropyl)methylcarbamate

Et3N (8.3 g, 0.082 mol) was added to a 0° C. solution of I2 (10.43 g, 0.041 mol), PPh3 (10.76 g, 0.041 mol) in CH2Cl2 (250 mL). The mixture was allowed to warm to rt. After stirring at rt for 0.5 hr, tert-butyl(1-(2-((5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinecarbonyl)cyclopropyl)methylcarbamate (10 g, 0.0205 mol) was added. The mixture was stirred at rt for another 1 hr. The mixture was concentrated, EtOAc (250 mL) was added, and the mixture was filtered to remove Ph3PO. The filtrate was concentrated and the residue was purified by silica gel column chromatography (gradient elution 33˜50% EtOAc/petroleum ether) to afford tert-butyl (1-(5-((5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)cyclopropyl)methylcarbamate (8 g, 83%) as a white solid. ESI-MS (EI+, m/z): 470.3 [M+H]+.

1. stirringThe mixture was stirred at rt for another 1 hr
2. concentrationThe mixture was concentrated
3. additionEtOAc (250 mL) was added
4. filtrationthe mixture was filtered
5. customto remove Ph3PO
6. concentrationThe filtrate was concentrated
7. customthe residue was purified by silica gel column chromatography (gradient elution 33˜50% EtOAc/petroleum ether)

ORD-Eintrag

ord-6e780eaa06184fc98ae6dd6abd98b651

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08962843B2