Water → HCID 70183914, Verbindung

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a suspension of (1S,2R)-3-(3,4-dichlorophenyl)-1-methyl-2-(2-naphthoyloxy)propylamine hydrochloride (42.5 mg, 0.10 mmol), prepared by the procedures described in European Patent Application EP 611749, published Aug. 24, 1994, and incorporated herein by reference, 1,2,3,4-cyclobutanetetracarboxylic dianhydride (100 mg, 0.50 mmol) in 1:1 etheracetonitrile (10 mL) at -78° C. was added triethylamine (15 mg, 0.15 mmol). The reaction mixture was allowed to warm to 22° C. overnight and then cooled with an ice-water bath. Diazomethane in ether was added to it until the solution remained slightly yellow. Formic acid (0.5 mL) was added immediately, followed by ethyl acetate (60 mL) and water (5 mL). The organic layer was washed with water (5 mL) and brine (5 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified with column chromatography eluting with ethyl acetate (80 mL), followed by 95:5:1 ethyl acetate-methanol-formic acid to give the title compound (51.3 mg). The proton NMR showed about a 1:1 ratio of rotomers. 1H NMR (300 MHz, DMSO-D6) δ 8.59, 8.55 (s, 1H), 8.37, 8.27 (d, 1H), 8.16-7.89 (m, 4H), 7.70-7.45 (m, 3H), 7.25 (t, 1H), 5.33 & 5.19 (m, 1H), 4.10 (m, 1H), 3.62 (s, 3H), 3.57-3.45 (m, 3H), 3.35 (m, 1H), 3.08 (m, 1H), 2.97 (m, 1H), 1.09, 1.07 (s, 3H). MS (FAB+) m/e 616 [35Cl, M+H]+.

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