2,3-Dihydroxybutanedioic Acid → (2s,3r)-n-(2-((3-Pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide d-tartrate salt

Participants

Reaction Steps

Tartaric acid (25.6 mg, 0.173 mmol) was added to a solution of (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide (125 mg, 0.346 mmol) in hot ethanol (1 mL). The resulting solution was slowly cooled to ambient temperature. No solids precipitated, so the solution was concentrated to give a white foam. Attempts to crystallize in isopropanol failed. The foam was dissolved in methanol and another half-equivalent of tartaric acid (25.6 mg, 0.173 mmol) was added. The mixture was concentrated to give a white foam, which would not crystallize from mixtures of methanol and isopropanol. The concentrated material (mixture of solid and gummy liquid) was then slurried in ethyl acetate (1 mL), producing a white solid. This was isolated by filtration (ethyl acetate wash) and drying in a vacuum oven (18 h at 40° C.), to give 141 mg (79.7% yield) of the mono stoichiometry salt (NMR), mp 136-140° C. Chiral LC analysis gave a purity of 98.1% (270 nm). 1H NMR (300 MHz, D2O) δ 8.50 (s, 1H), 8.01 (d, 1H), 7.86 (d, 1H), 7.75 (d, 1H), 7.56 (m, 2H), 7.38 (t, 1H), 7.32 (s, 1H), 7.21 (t, 1H), 4.34 (s, 2H, tartaric acid), 4.26 (d, 1H), 3.95 (m, 1H), 3.64 (m, 2H), 3.15-3.55 (m, 4H), 1.90-2.30 (m, 5H).

Provenance & Evidence