Potassium Carbonate → Isopropyl [4-(diphenylmethylidene)piperidin-1-yl]ethanoate

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A mixture of amine 20 (779 mg, 3.12 mmol), isopropyl bromoacetate (575 mg, 3.18 mmol), K2CO3 (1.34 g, 3 eq), and acetonitrile (28 mL) was stirred at reflux overnight. The reaction mixture was filtered, evaporated to dryness, and then chromatographed over silica gel using 5:1 heptane/EtOAc to give 0.78 g of 15d as an oil that crystallized on standing. The structure was confirmed by 1H NMR. (Acetate esters 15b and 15c were similarly prepared.) Cyclopentyl [4-(diphenylmethylidene)piperidin-1-yl]ethanoate (15e). A solution of 15b (1.02 g, 3.17 mmol) in anhydrous THF (10 mL) was added (under N2) to a mixture of isobutyl alcohol (10 mL) and sodium hyride (258 mg of a 60% oil dispersion). After stirring for 1 h, the reaction mixture was partitioned between water and EtOAc, wherein a small amount of brine was added to prevent emulsion formation. The organic layer was then removed, the aqueous layer was extracted further with EtOAc, and the combined organics were dried with Na2SO4, filtered, and evaporated to dryness. Chromatography over silica gel using 5:1 heptane/EtOAc gave 0.8 g of 15e as an oil. (Acetate ester 15f was similarly prepared.) Isopropyl [4-(diphenylmethylidene)piperidin-1-yl]ethanoate, oxalic acid salt (15d-oxalate). A solution of oxalic acid (234 mg, 2.6 mmol) in ethanol (4 mL) was added dropwise to a stirred solution of 15d (910 mg, 2.6 mmol) in ethanol (12 mL). After cooling the reaction mixture to −15° C. for 15 min, the solid was filtered, washed with cold ethanol, and vacuum dried to give 891 mg of 15d-oxalate as a white crystalline solid. The structure of the product was confirmed by 1H NMR, MS, and elemental analysis. (The oxalate salts of 15c, 15e, and 15f were similarly prepared.)

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