2,3,5-Tri-O-benzyl-1-O-(4-nitrobenzoyl)-D-arabinofuranose → Fludarabine

A solution of 2,3,5-tri-O-benzyl-1-α-D-arabinofuranosylchloride (freshly prepared from 1.9 g of 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose) and 6-azido-2-fluoropurine (0.50 g) in anhydrous acetonitrile (30 mL) was stirred for 1 hour at room temperature and then 3 Å molecular sieve (1.26 g, pellets) was added. The mixture was stirred under an inert atmosphere for 3 days and then filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in 2-propanol and methanol, and then sodium borohydride (0.13 g) was added. After stirring overnight at room temperature the resulting precipitate was collected by filtration. The precipitate was washed with 2-propanol followed by boiling water and then dried to obtain 0.14 g of the title compound. The organic filtrates were concentrated under reduced pressure and the residue was partitioned between dichloromethane and water. The dichloromethane solution was dried over MgSO4 and then filtered and placed on a silica gel column. Elution with 1% methanol in dichloromethane provided an additional 0.10 g of the title compound. Both samples were identical by IR and TLC to an authentic sample of the title compound.

1. addition3 Å molecular sieve (1.26 g, pellets) was added
2. stirringThe mixture was stirred under an inert atmosphere for 3 days
3. filtrationfiltered
4. concentrationThe filtrate was concentrated under reduced pressure
5. dissolutionthe residue was dissolved in 2-propanol
6. additionmethanol, and then sodium borohydride (0.13 g) was added
7. stirringAfter stirring overnight at room temperature the resulting precipitate
8. filtrationwas collected by filtration
9. washThe precipitate was washed with 2-propanol
10. customdried

ORD-Eintrag

ord-ef3ac05e51044f00a5f720756c378cea

Quelldatensatz

uspto-grants-1993_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05180824