Tetrafluoroboric acid → HCID 44323403, compound

Participants

Reaction Steps

The above 2',3',5'-tri-O-acetyl-N-(1-piperidinyl)adenosine (1.33 g, 2.7 mmol) was dissolved in THF (50 ml) and the temperature of the solution was held between -10° C. and -20° C. Fluoroboric acid (48%, 100 ml) was added followed by an aqueous solution of sodium nitrite (0.75 g/ml, 1.5 ml). Addition of three identical amounts of sodium nitrite was continued at 0.3 hour intervals, after which TLC investigation (on a neutralised sample) indicated that the starting material was consumed [rf 0.47 (SiO2, ethyl acetate/methanol (90/10))]. The pH of the reaction mixture was adjusted to ca. 6 with 50% sodium hydroxide solution with cooling to below 0° C. and the now red reaction mixture was diluted with water (250 ml). The solution was extracted with chloroform (2×100 ml) and the combined extracts were dried (MgSO4). The residue on evaporation (containing 2',3',5'-tri-O-acetyl-2-fluoro-N-(1-piperidinyl)adenosine was treated with methanolic ammonia (150 ml) (previously saturated at -10° C.) and stirred at room temperature for 72 hours. The reaction mixture was evaporated and the resultant residue was purified by column chromatography on silica gel eluting with dichloromethane/methanol (0-10%) to provide the title compound (0.093 g) as a white solid, after washing with ethyl acetate. M.p. 197°-199° C.; 1H NMR (400 MHz, Me2SO-d6) δ 3.57, 3.65 (2H, ABX, H-5'a and H-5'b), 3.92 (1H, q, H-4'), 4.12 (1H, m, H-3'), 4.50 (1H, q, H-2'), 5.80 (1H, d, H-1'), 8.35 (1H, s, H-8). HPLC retention time 10.12 (gradient elution, 5-25% acetonitrile/0.1M pH 3.3 ammonium sulphate buffer: 214 nm detector): 100% purity.

Provenance & Evidence