Sodium Hydroxide → 9-(2,3,5-Tri-O-benzyl-beta-D-arabinofuranosyl)-2-fluoroadenine

Participants

Reaction Steps

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).

Provenance & Evidence