Sodium Hydroxide → 9-((2R,3S,4R,5R)-3,4-Bis(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-yl)-2-fluoro-9H-purin-6-amine

HBF4 (48%) (150 ml) was added to a solution (5°) of 2-amino-9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)adenine (III, 4.6 g, 8.4 mmol) in CHCl3 (60 ml). The resulting mixture was cooled to -10° before a solution of N--NO2 (17 g, 25 mmol) in 4 ml of H2O was added dropwise with stirring. After the addition was complete, the mixture was stirred an additional 40 min. at -10° to -5° before it was diluted with CHCl3 (75 ml), cooled to -20°, and neutralized (pH 5-6) with 50% NaOH. The CHCl3 layer was separated, washed with H2O, dried (MgSO4), and evaporated to dryness in vacuo. The residue, primarily a mixture of II and 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2,6-difluoropurine, identified by TLC (1:1 CHCl3 -EtOAc), was dissolved in absolute EtOH, and the solution was saturated at 5° with dry NH3. After refrigeration overnight, the reaction solution was evaporated to dryness in vacuo. The residue was dissolved in CHCl3 (25 ml), and the solution was filtered through dry Celite to remove inorganic salts. The filtrate was adsorbed on a silica gel column (2.6×35 cm, packed and equilibrated with CHCl3). The column was eluted with 1:1 CHCl3 -EtOAc. The fractions containing II were combined and evaporated to dryness in vacuo, and the residue was recrystallized from C6H6 (40 ml); yield 1.7 g (36%); mp 157°-159°; λmax (mμ), pH 1, 7, 13, and EtOH--261, 272 (sh); vmax (cm-1) 3350, 3320, 3150 (NH), 2940, 2920, 2910, 2860 (CH), 1665, 1610, 1575 (NH, C=C, C=N), 1110, 1100, 1085, 1060 (COC), 730 (phenyl).

1. additionwas added dropwise
2. additionAfter the addition
3. stirringthe mixture was stirred an additional 40 min. at -10° to -5° before it
4. temperaturecooled to -20°
5. customThe CHCl3 layer was separated
6. washwashed with H2O
7. dry with materialdried (MgSO4)
8. customevaporated to dryness in vacuo
9. additionThe residue, primarily a mixture of II and 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2,6-difluoropurine
10. dissolutionwas dissolved in absolute EtOH
11. customwas saturated at 5° with dry NH3
12. customthe reaction solution was evaporated to dryness in vacuo
13. dissolutionThe residue was dissolved in CHCl3 (25 ml)
14. filtrationthe solution was filtered
15. customthrough dry Celite
16. customto remove inorganic salts
17. washThe column was eluted with 1:1 CHCl3 -EtOAc
18. additionThe fractions containing II
19. customevaporated to dryness in vacuo
20. customthe residue was recrystallized from C6H6 (40 ml)

ORD-Eintrag

ord-ec473e4b54b24c5dab27491673679f55

Quelldatensatz

uspto-grants-1980_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04188378