p-Toluenesulfonic acid → Ethyl 11-bromoundecanoate

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This example is a method of synthesis for inventive compound no. 3549 (see above for chemical name and structure). A solution of 11-bromoundecanoic acid (5.70 g, 22 mmol, available from Aldrich) and p-toluenesulfonic acid (0.1 g) in absolute ethanol (100 ml) was refluxed for 3 hours. A saturated aqueous sodium bicarbonate solution (40 ml) was added and the reaction mixture then extracted with three 70 ml aliquots of dichloromethane. The combined extracts were washed with water (50 ml) and saturated aqueous salt solution (50 ml) and the solvent was evaporated, leaving a colorless oil. Ethyl 11-bromoundecanoate (5.92 g, 94% yield) was collected during distillation (2 mm) at 135° C. A solution of this bromoester (5.92 g, 20 mmol) and 1-sodiotheobromine (4.08 g, 20 mmol) in dimethylsulfoxide (80 ml) was stirred for 18 hours at ambient temperature. The mixture was added to water (100 ml) and dichloromethane (100 ml). The aqueous layer was extracted with two 80 ml aliquots of dichloromethane. The combined organic layers were washed with water (80 ml) and saturated aqueous salt solution (80 ml), dried over magnesium sulfate, and the solvent was evaporated under vacuum, leaving a white solid residue. The residue was recrystallized in dichloromethane/ether/hexane, yielding 4.95 g of 1-(ethyl 11-yl-undecanoate)-3,7-dimethylxanthine (62% yield).

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