Reaction Steps
To a stirred suspension of 7,8-dichloro-3-methoxy-6-methyl-6,7,8,9-tetrahydro-1H-1-benzazepine-2,5-dione (120 mg, 413 μmol) in dry CH2Cl2 (20 mL, distilled from CaH2) under N2, there was added a solution of BBr3 in CH2Cl2 (2.5 mL, 1M, Aldrich) in one portion over 5 seconds at rt. The suspension immediately turned green. The reaction was allowed to stir under N2 at rt for 1 h. The reaction was added to saturated NaHCO3 (50 mL) and the resulting pale pink suspension was vigorously stirred for 15 min to give an emulsion. The emulsion was vacuum filtered and the resulting pink aqueous solution washed with CH2Cl2 (1×10 mL). The aqueous portion was acidified with concd HCl (pH 2). The resulting precipitate was collected by filtration and washed to neutrality with water (6×2 mL). Crystallization of the damp filter cake from 95% EtOH (dissolved in boiling solvent (45 mL), hot filtered, allowed to cool to rt) yielded a colorless, fluffy solid (67 mg, 59%, pure by 1H NMR, probable mixture of diastereomers (9 to 1)); mp 180°-181° C. (dec.); 1H NMR (DMSO-d6 and D2 O) δ1.17 (d, J=6.9 Hz, 3H), 2.97 (dd, J1 =17.4 Hz, J2 =9.6 Hz, 1H), 3.13 (dd, J1 =17.4 Hz, J2 =4.8 Hz, 1H), 3.22 (m, 1H), 4.13 (dd, J1 =9.3 Hz, J2 =6.6 Hz, 1H), 4.38 (m, 1H), 6.32 (s, 1H), the spectrum without D2O shows additional resonances δ10.47 (bs, 1H), 11.01 (s, 1H); IR (KBr) 3301 (m), 3207 (w), 3165 (w), 3093 (m), 2987 (m), 1680 (m), 1648 (m), 1613 (m), 1553 (s), 1463 (w), 1447 (w), 1425 (w), 1401 (m), 1345 (m), 1319 (w), 1285 (m), 1227 (m), 1164 (w), 1123 (w), 1054 (w), 1020 (w), 934 (w), 911 (m), 861 (w), 810 (m), 770 (m), 754 (m), 717 (m), 667 (w), 656 (w), 621 (w), 494 (w) cm-1 ; Anal. Calcd for C11H11Cl2NO3 : C, 47.85, H, 4.02, N, 5.07. Found: C, 48.00; H, 3.85; N, 5.20. ##STR155## The binding data imply that compounds of Formula IX having a combination of substituents other than H at R1, R3 and R4 are preferred.
