Sodium hydride → (R)-1-(5-Acetoxyhexyl)-3-(2-furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine

Participants

Reaction Steps

To a stirring solution of 3-(2-Furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine (0.65 g, 1.8 mmol) in dimethyl sulfoxide (20 ml) was added sodium hydride in one portion. After 30 minutes, (R)-5-acetoxy-1-iodohexane (0.58 g, 2.16 mmol, prepared as above) was added neat. The reaction was allowed to stir at ambient temperature for 20 hours, quenched with water (70 ml) and then extracted with ethyl acetate (3×35 ml). The extracts were washed with saturated aqueous sodium chloride solution (30 ml), dried over sodium sulfate and concentrated to give a crude yellow oil. The product was purified by flash chromatography on silica gel (ethyl acetate) to give (R)-1-(5-Acetoxyhexyl)-3-(2-furylmethyl)-7-pivaloyloxymethyl-8-methylxanthine (0.41 g) as a yellow oil. The product oil was dissolved in methanol (20 ml) and treated with a sodium methoxide solution (25 wt. % in MeOH, 0.94 ml, 4.1 mmol). The reaction was allowed to stir at ambient temperature for 48 hours. The solution was diluted with ethyl acetate (40 ml) and quenched with water (20 ml). The organic phase was collected and washed with saturated aqueous sodium chloride solution (20 ml), dried over sodium sulfate and concentrated to give a yellow solid. Column chromatography on silica gel eluting with 10% methanol-ethyl acetate gave (R)-3-(2furylmethyl)-1-(5-hydroxyhexyl)-8-methylxanthin CT2412R (21 mg) as an off-white solid.

Provenance & Evidence