8-(2-Chloroethyl)-8-azaspiro[4.5]decane-7,9-dione → 8-{2-[4-(2,5-Difluorophenyl)piperazin-1-yl]ethyl)-8-azaspiro[4.5]decane-7,9-dione

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A mixture of 1-(2,5-difluorophenyl)piperazine (100 mg, 0.51 mmol) and 8-(2-chloroethyl)-8-azaspiro[4.5]decane-7,9-dione (100 mg, 0.44 mmol) was heated with stirring at 160° C. for 5 hours. The residue was dissolved in methanol, transferred to a preparative thin layer chromatographic plate (silica gel), and eluted with ethyl acetate/hexane (1:1). A band at Rf=0.7 was removed and rinsed with chloroform/methanol (4:1). The solvent was removed, giving the title compound as a pale yellow oil. 1H NMR (300 MHz, CDCl3) δ6.99-6.89 (11-line m, 1H), 6.65-6.52 (m, 2H), 3.95 (t, 2H, J=6.5 Hz), 3.03 (t, 4H, J=4.7 Hz), 2.66 (t, 4H, J=4.7 Hz), 2.60 (s, 4H), 2.54 (t, 2H, J=6.6 Hz), 1.74-1.69 (m, 4H), 1.55-1.51 (m, 4H); ESI-MS m/z 392 (MH+). The title compound was dissolved in ether and precipitated by addition of 1N HCl in ether, giving a white solid (64.9 mg, 0.15 mmol, 35%): mp 237-239° C., Anal. Calcd. for C21H27N3F2O2·HCl: C, 58.94; H, 6.59; N, 9.82; F, 8.88. Found: C, 58.70; H, 6.46; N, 9.68; F, 9.00.

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