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

Participants

Reaction Conditions

Reaction Steps

To a stirring suspension of 7-benzyl-3-methylxanthine (25.6 g, 100 mmol) (which had been prepared as described for CT22404 of Example 18) in dimethylsulfoxide (200 ml) was added 95% sodium hydride (3.2 g, 133 mmol) in portions over 10 minutes. After stirring for 30 minutes, (R)-5-acetoxy-1-chlorohexane (19.63 g, 110 mmol) was added neat. After heating at 70-80° C. for 6 hours, the reaction mixture was quenched by addition of water (500 ml) and extracted with ethyl acetate (3×150 ml). The combined extracts were washed with water (150 ml), saturated aqueous sodium chloride solution (150 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 20% hexane/ethyl according to give (R)-1-(5-acetoxyhexyl)-7-benzyl-3-methylxanthine (33.7 g).

Provenance & Evidence