Reaction Steps
The ester 198 (4.0 g, 11.8 mmol) was added in small portions to a stirred solution of 70% HNO3 (2 mL acid/g of substrate) at room temperature and the reaction mixture was allowed to stir overnight. After 16 hours TLC (CHCl3) revealed the complete loss of starting material. The reaction mixture was cooled in an ice bath, and 15 g of iced water was added, precipitating the product. The precipitate was collected by vacuum filtration and washed with small amount of iced water. The filtrate was cooled and a second crop of precipitate was collected by vacuum filtration and washed with iced water. The combined precipitate was dried in vacuo to provide compound 199 as a yellow solid, which was not purified further, but used directly in the subsequent reaction (2.3 g, 70%). mp=101-103° C.; 1H-NMR (CDCl3/DMSO-d6, 270 MHz): δ 2.31 (m, 2H, H2′), 3.20 (br, 2H, H3′), 3.95 (s, 3H, OCH3 ether), 3.98 (s, 3H, OCH3ester), 4.24 (t, 2H, J=5.95 Hz, H1′), 7.11 (s, 1H, H6), 7.49 (s, 1H, H3), 8.21 (s, 3H, NH); 13C-NMR (CDCl3, 68.7 MHz): δ 26.5 (C2′), 37.0 (C3′), 53.0 (OCH3ester), 56.0 (OCH3ether), 66.7 (C1′), 108.3 (C3), 111.0 (C6), 121.6 (Carom), 140.9 (C2), 149.3 (Carom), 152.6 (Carom), 166.8 (C═O); Ms (E/I) m/z (relative intensity): 284 (M+., 90), 237 (70), 227 (93), 196 (47), 181 (38), 137 (100), 122 (81), 93 (52), 79 (44); HRMS (E/I) exact mass calcd for C12H17N2O6: m/e 284.1008, obsd m/e 284.1018; IR (Nujol®) n: (cm−1) 3472, 2937, 2911, 2855, 1733, 1532, 1516, 1462, 1377, 1292, 1224, 1143, 1052, 884, 812, 792, 773, 756, 724, 646.
