Reaction Steps
A flask equipped with a Dean-Stark apparatus was charged with trifluoro-methanesulfonic acid (7aR,11aS)-11a-ethyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cyclohepten-3-yl ester; compound with trifluoro-methanesulfonic acid (7 aS,11aR)-11a-ethyl-9-oxo-6,7,7a,8,9,10,11,11a-octahydro-5H-dibenzo[a,c]cyclohepten-3-yl ester (19, R2=Ethyl) (2.2 g, 5.63 mmol), ethane-1,2-diol (1.571 mL, 28.2 mmol), pTSA (0.107 g, 0.563 mmol) and toluene (44 mL). The mixture was heated to reflux for about 21 h. The mixture was cooled to rt, EtOAc (20 mL), sat. aq. NaHCO3 (10 mL) were added and the layers were separated. The organic layer was washed with brine (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (12 g) using a gradient of 0-40% EtOAc in heptane. Product fractions were combined and concentrated under reduced pressure to yield rac-(4aR,11bS)-11b-ethyl-1,2,4,4a,5,6,7,11b-octahydrospiro[dibenzo[a,c][7]annulene-3,2′-[1,3]dioxolan]-9-yl trifluoromethanesulfonate (20, R2=Ethyl) (2.2 g, 90%); LC/MS, method 3, Rt=3.05 min, MS m/z 435 (M+H)+. 1H NMR (400 MHz, DMSO) δ 7.42-7.35 (m, 1H), 7.26-7.22 (m, 2H), 3.91-3.69 (m, 4H), 3.04-2.77 (m, 2H), 2.43-2.37 (m, 1H), 2.22-2.13 (m, 1H), 2.11-1.94 (m, 2H), 1.71-1.62 (m, 2H), 1.61-1.54 (m, 2H), 1.52-1.35 (m, 3H), 1.32-1.17 (m, 2H), 0.59 (t, J=7.4 Hz, 3H).
