Reaction Steps
A flask with stir bar and nitrogen line was charged with rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-yl trifluoromethanesulfonate (144, R2=Pyridin-2-ylmethyl) (9.14 g, 18.34 mmol) (assumed 100% for previous reaction), (E)-styrylboronic acid (3.39 g, 22.9 mmol), cesium carbonate (14.94 g, 45.9 mmol), 1,4-dioxane (130 mL), water (32.5 mL) and bis(triphenylphosphine)palladium(II) dichloride (0.644 g, 0.917 mmol). The mixture was warmed in an oil bath heated to about 90° C. for about 30 min. The mixture was cooled then concentrated under reduced pressure. The material was partitioned between water (100 mL) and EtOAc (100 mL). The layers were separated then the organic solution was washed with brine (75 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The filtrate was concentrated under reduced pressure then the material was purified on silica gel (330 g) using 100% EtOAc. Product fractions were combined and concentrated under reduced pressure to yield (7aR,11aS)-11a-(pyridin-2-ylmethyl)-3-((E)-styryl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane] (145, R2=Pyridin-2-ylmethyl) (6.15 g, 74%); LC/MS, method 3, Rt=2.50 min, MS m/z 453 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 8.14 (s, 1H), 7.59-7.52 (m, 3H), 7.38-7.35 (m, 2H), 7.33-7.05 (m, 4H), 6.97-6.94 (m, 1H), 6.23 (s, 1H), 4.04-3.90 (m, 4H), 3.49 (d, J=13.8 Hz, 1H), 3.39-3.29 (m, 1H), 3.25 (d, J=13.3 Hz, 1H), 2.97-2.89 (m, 1H), 2.28-2.20 (m, 1H), 2.11-1.96 (m, 4H), 1.92-1.86 (m, 1H), 1.84-1.70 (m, 2H), 1.69-1.48 (m, 3H).
