Dimethylformamide → N-2-adamantyl-4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxamide

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Reaction Steps

Carboxylic acid 2-8 (0.100 g, 0.348 mmol) was dissolved in 2 mL of anhydrous methylene chloride under nitrogen atmosphere, treated with oxalyl chloride (2 M in methylene chloride, 2 eq., 0.348 mL, 0.696 mmol) and subsequently with 0.050 ml of DMF. The reaction was stirred at room temperature under nitrogen atmosphere for 90 min, then evaporated and placed under vacuum for 20 min. The acid chloride was dissolved in anhydrous methylene chloride (2 mL), and then treated with triethylamine (0.100 ml) and 2-adamantylamine (2 eq., 105 mg). The reaction stirred at ambient temperature for 1 hr. The mixture was diluted with 20 mL of methylene chloride and washed with 1N aqueous HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated. The product was purified using a Gilson HPLC with UV detection equipped with a C18 reverse phase column running a gradient of water/acetonitrile (0.1% TFA). The fractions containing product were concentrated to remove some of the acetonitrile and the lyophilized to provide pure product N-2-adamantyl-4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]octane-1-carboxamide (2-9) as a white fluffy amorphous solid.

Provenance & Evidence