A mixture of 8-phenyl-5-oxa-7-azaspiro[3.4]octan-6-one (0.3 g, 1.57 mmol), 4-iodo-N-(quinolin-8-yl)benzamide, (0.650 g, 1.73 mmol), Cs2CO3 (1.125 g, 3.47 mmol), X-Phos (40 mg, 0.07 mmol) and Pd2(dba)3 (73 mg, 0.07 mmol) in 1,4-dioxane (2 mL) in a 50 mL round bottom flask was purged with N2 gas for 15 minutes. The reaction mixture was then heated at 90° C. for 12 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the reaction mixture was cooled, and 1,4-dioxane was evaporated under reduced pressure to afford initial product. The initial product was purified by column chromatography using silica gel eluting with 20% EtOAc in hexane to yield (R+S) 4-(6-oxo-8-phenyl-5-oxa-7-azaspiro[3.4]octan-7-yl)-N-(quinolin-8-yl)benzamide (70 mg, 12%) as a brown solid. 1H NMR (400 MHz, CDCl3) δ: 10.65 (s, 1H), 8.88 (dd, J=7.2, 1.6 Hz, 1H), 8.83-8.81 (m, 1H), 8.18 (dd, J=8.4, 1.6 Hz, 1H), 7.99-7.96 (m, 2H), 7.67-7.64 (m, 2H), 7.59-7.51 (m, 2H), 7.49-7.45 (m, 1H), 7.43-7.34 (m, 3H), 7.29-7.26 (m, 2H), 5.23 (s, 1H), 2.68-2.63 (m, 1H), 2.48-2.43 (m, 1H), 2.22-2.18 (m, 1H), 1.96-1.91 (m, 1H), 1.76-1.71 (m, 1H), 1.62-1.57 (m, 1H). m/z (ESI) 450.1 (M+H)+.
