Reaction Steps
Concentrated nitric acid (5 mL) was added dropwise to a mixture of concentrated sulfuric acid (5 mL), 12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-3,12-dicarboxylic acid 12-ethyl ester 3-methyl ester (300 mg, 1.04 mmol) and CH2Cl2 (5 mL) at 0° C. The resulting brown solution was stirred at this temperature for 30 min before pouring onto ice-water and extracting with CH2Cl2 (2×5 mL). Drying over MgSO4, filtering and concentration gave a brown residue that was purified with silica gel chromatography (0-20% EtOAc in hexanes) to give 6-Nitro-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-4,12-dicarboxylic acid 12-ethyl ester 4-methyl ester as a clear oil (81 mg, 23%) 1HNMR (400 MHz, CDCl3) δ 8.5 (s, 1H), 8.0 (s, 1H), 5.2 (m, 1H), 4.7 (m, 1H), 4.1 (q, 2H, J=7.1 Hz), 4.0 (s, 3H), 3.6-3.5 (m, 1H), 3.0 (d, 1H, J=18.7), 2.3-2.2 (m, 2H), 1.9 (m, 1H), 1.7 (m, 1H), 1.3-1.2 (m, 3H); MS (m/e) 335 (M+1); and 5-Nitro-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-4,12-dicarboxylic acid 12-ethyl ester 4-methyl ester as a pale yellow solid (79 mg, 23%) as the 5-nitro compound. 1HNMR (400 MHz, CDCl3) δ 7.6 (s, 1H), 7.4 (s, 1H), 5.1 (m, 1H), 4.6 (m, 1H), 4.1 (q, 2H, J=7.3 Hz), 3.9 (s, 3H), 3.5-3.4 (m, 1H), 2.7 (d, 1H, J=17.4), 2.3-2.2 (m, 2H), 1.9 (m, 1H), 1.7 (m, 1H), 1.3-1.2 (m, 3H); MS (m/e) 335 (M+1); The regioisomers were distinguished by NOE and 1H-1H COSY
