Methane → Fludarabine

Participants

Reaction Steps

Boron trichloride gas was bubbled in methylene chloride (610 ml.) at 0° in a 2-l., 3-necked flask equipped with a thermometer, magnetic stirrer, and addition funnel and the stirred solution then cooled to -72° (dry ice-acetone) before the dropwise addition (1 hour) of a cold solution of 9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2-fluoroadenine (6, 7.0 g., 12.5 mmoles) in methylene chloride (70 ml.). After a total reaction time of 2.75 hours, the cooling bath was removed and the solvent and gas removed in vacuo. The residue was dissolved in cold methylene chloride (40 ml.) and the solution evaporated to dryness (6 times) or until a solid white residue was obtained, before adding 450 ml. of cold 5% sodium bicarbonate followed by solid sodium bicarbonate to adjust the pH to 6-7. The mixture was diluted with ethanol, heated to boiling, treated with charcoal, filtered through Celite, and then allowed to stand at room temperature overnight. It was then chilled and the solid collected by filtration, washed with cold water and then ether, and dried in vacuo; yield 3.23 g. (91%); m.p. 259°-260°; homogeneous according to tlc (19:1) and hplc (23 water:2 acetonitrile); nmr: 3.7 (m, H4' and 2H5'), 4.15 (m, H2' and H3'), 5.1 (t, 5'--OH), 5.55 and 5.65 (2d, 2'-13 OH and 3'--OH), 6.14 (d, J'2' 3 Hz, H1'), 7.8 (broad s, NH2), 8.2 (s, H8); uv: pH 1-262 (13.2); pH 7, 13-261 (15.3).

Provenance & Evidence