Sodium hydride → (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine

Participants

Reaction Steps

To a stirring suspension of 7-benzyl-3-methylxanthine (11.1 g, 43.2 mmol) in dimethyl sulfoxide (100 ml) was added 95% sodium hydride (1.24 g, 52 mmol) in one portion. After stirring for 30 minutes, (R)-5-acetoxy-1-bromohexane (8.1 g, 45.3 mmol) was added neat. The (R)-5-Acetoxy-1-bromohexane was prepared according to methods described in U.S. Pat. No. 6,075,029 issued to Klein, J. P., Kumar, A. M., and Woodson, P on Jun. 13, 2000, which is incorporated herein by reference. After stirring at 80° C. for 16 hours and cooled to room temperature, the reaction was quenched by addition of water (350 ml) and extracted with ethyl acetate (5×50 ml). The combined extracts were washed with saturated aqueous sodium bicarbonate solution (50 ml), with saturated aqueous sodium chloride solution (50 ml) and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave a residue which was purified by flash chromatography on silica gel eluting with ethyl acetate to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine (13.0 g, 76% yield).

Provenance & Evidence