Reaction Steps
Trimethylsilyldiazomethane (0.12 mL, 2.0 M in diethyl ether, 0.25 mmol) was added dropwise to a suspension of 22 (110 mg, 0.19 mmol) in methanol (1 mL) and THF (3 mL) at −10 to 0° C., and the mixture was stirred at −10° C. for 30-45 min after addition. The solvent was removed under reduced pressure at 20-25° C. The residue (24, cis-trans mixture) was dissolved in anhydrous 1,4-dioxane (5 mL) and DDQ (100 mg, 0.44 mmol) was added to the solution. The reaction mixture was heated at reflux for 3-4 h. 1,4-Dioxane was evaporated under reduced pressure and chloroform (30 mL) was added to the residue. The mixture was washed with sodium bicarbonate (5%, 2×10 mL), water (15 mL), dried with sodium sulfate, and filtered through a thin layer of silica gel, eluting with chloroform. The combined filtrates were evaporated under reduced pressure. The amorphous solid containing 26 was added to a stirred solution of KOH (180 mg, 18.5 mmol) in water-ethylene glycol mixture (1+3 mL) at room temperature, and the mixture was heated at reflux on oil bath for 24 h. After the mixture was cooled to room temperature, it was diluted with water (5 mL) and acidified with acetic acid (0.5 mL). The white precipitate was collected by filtration to obtain 28 as a white powder (24 mg, 47%): mp 313° C. IR (KBr) 1650, 1604 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 11.85 (s, 1 H), 9.36 (s, 1 H), 8.02 (d, J=8.3 Hz, 1 H), 7.71 (s, 1 H), 7.54 (t, J=7.6 Hz, 1 H), 7.44 (d, J=8.1 Hz, 1 H), 7.23 (t, J=7.6 Hz, 1 H), 4.51 (t, J=6.8 Hz, 2 H), 4.43 (t, J=4.8 Hz, 1 H), 3.92 (s, 3 H), 3.91 (s, 3 H), 3.22 (dd, J=10.8, 5.5 Hz, 2 H), 2.05-1.81 (m, 2 H); 13C NMR (126 MHz, DMSO-d6) δ 162.82, 160.88, 152.96, 149.17, 144.41, 137.37, 130.28, 128.54, 126.19, 121.07, 118.95, 115.89, 113.14, 107.83, 107.40, 57.90, 55.63, 55.50, 48.77, 31.35; positive ESIMS m/z (rel intensity) 381 (MH+, 100). Anal. Calcd for C21H20N2O5: C, 66.31; H, 5.30; N, 7.36. Found: C, 66.03; H, 5.16; N, 7.26.
