Beilstein J. Org. Chem. 2014, 10, 2594–2602.
89.22 mmol) was added in two parts and the mixture was stirred toluene was removed under reduced pressure. The residue was
for 6 h. Cold diethyl ether (200 mL) was added to the reaction purified by column chromatography on silica gel (ethyl acetate/
mixture and stirring was continued for 1 h. The precipitated hexane 4:1) to give rac-5 as yellow solid (1.77 g, 71%). Mp
white solid was filtered and refluxed in 180 mL water for 3 h. 152–156 °C; 1H NMR (400 MHz, CDCl3) δ 3.63 (dd, J = 10.8
After cooling to room temperature, it was refrigerated for 1 h, and 13.6 Hz, 3-Hax, 1H), 4.04 (dd, J = 13.6 and 2.4 Hz, 3-Heq,
the resultant precipitate was filtered and washed with cold 1H), 4.71 (d, J = 16.4 Hz, 5-Ha, 1H), 4.94 (d, J = 16.4 Hz, 5-Hb,
water. The product rac-9 was dried and isolated as white 1H), 5.29 (dd, J = 10.8 and 2.4 Hz, 2-H, 1H), 7.03 (m, J = 9.6
powder (8.23 g, 77%) with mp 127–129 °C. 1H NMR (400 Hz, 6-H, 9-H, 2H), 7.13 (m, 8-H, 1H), 7.26 (m, 6”-H, 7-H, 2H),
MHz, CDCl3) δ 3.54 (m, 3-Ha, 1H), 3.66 (m 3-Hb, 1H), 5.46 7.36–7.42 (m, Ph, 5H), 8.17 (dd, J = 9.2 Hz and 2.8 Hz, 5”-H,
(dd, J = 9.7 and 3.6 Hz, 2-H, 1H), 7.07 (d, J = 8.4 Hz, 9-H, 1H), 1H), 8.61 (d, J = 2.8 Hz, 3”-H, 1H), 9.97 (s, CHO, 1H); 13C
7.19 (m, J = 7.6 Hz, 7-H, 1H), 7.28 (bs, NH, 1H), 7.36–7.44 (m, NMR (100 MHz, CDCl3) δ 56.1 (C-5), 64.6 (C-3), 82.7 (C-2),
Ph, 5H), 7.50 (m, J = 7.6 Hz, 8-H, 1H), 7.85 (dd, J = 8.0 and 117.6 (C-6”), 121.0 (C-9), 123.8 (C-7), 124.3 (C-5a), 125.9
1.6 Hz, 6-H, 1H); 13C NMR (100 MHz, CDCl3) δ 46.3 (C-3), (C-2’, C-6’), 127.5 (C-2’’), 128.1 (C-4”), 128.7 (C-8, C-3”),
85.8 (C-2), 122.4 (C-9), 123.7 (C-7), 125.9 (C-5a), 126.3 (C-2’, 129.1 (C-3’, C-5’), 129.5 (C-5”), 129.8 (C-4’), 129.8 (C-6),
C-6’), 128.5 (C-4’), 128.7 (C-3’, C-5’), 130.9 (C-6), 133.3 138.1 (C-1’), 156.8 (C-9a), 158.2 (C-1”), 188.3 (CHO); IR
(C-8), 139.0 (C-1’), 154.5 (C-9a), 170.9 (C-5); IR (KBr) ν: (KBr) ν: 1382, 1500, 1681, 1734, 2921 cm−1; HRMS–ESI
1462, 1665, 2917, 3075, 3203, 3307 cm−1; HRMS–ESI (m/z): (m/z): [M + Na]+ calcd for C22H18N2O4Na, 397.1164; found,
[M + Na]+ calcd for C15H13NO2Na, 262.0844; found, 397.1158; Anal. calcd for C22H18N2O4 (374.12): C, 70.58; H,
262.0839; Anal. calcd for C15H13NO2 (239.09): C, 75.30; H, 4.85; N, 7.48; found: C, 70.59; H, 4.89; N, 7.45.
5.48; N, 5.85; found: C, 75.28; H, 5.49; N, 5.85.
trans-1,3-Dimethyl-11'-nitro-2'-phenyl-1',2'-dihydro-
2-Phenyl-2,3,4,5-tetrahydro-1,4-benzoxazepine (rac-10): To 2H,7b'H,9'H-spiro[pyrimidine-5,8'-quinolino[1,2-
a stirred solution of rac-9 (8.13 g, 33.98 mmol) in dry THF d][1,4]benzoxazepine]-2,4,6(1H,3H)-trione (rac-trans-7a): To
(80 mL), 2.0 M lithium aluminium hydride solution in THF was a stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform
added dropwise (10 mL, 0.76 g, 20.03 mmol) and the mixture (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and 1,3-
was refluxed for 1.5 h. After cooling to room temperature, ethyl dimethylbarbituric acid (60 mg, 0.38 mmol) were added and the
acetate (5 mL), methanol (5 mL) and water (50 mL) were added mixture was refluxed for 4 h. After cooling to room tempera-
and the mixture was concentrated under reduced pressure. The ture, MgSO4 was filtered off and chloroform was removed
residue was extracted with dichloromethane (3 × 50 mL). The under reduced pressure. Water (10 mL) and dichloromethane
combined organic layers were washed with water (20 mL), (20 mL) were added and the layers were separated. The aqueous
dried over MgSO4, filtered and concentrated under reduced phase was extracted with dichloromethane (2 × 10 mL). The
pressure. The product rac-10 was isolated as yellow solid combined organic layers were washed with concentrated
(6.12 g, 80%) with mp 73–74 °C. 1H NMR (400 MHz, CDCl3) NaHCO3 solution, dried over MgSO4, filtered and concentrated
δ 3.20 (dd, J = 14.4 and 10.0 Hz, 3-Hax, 1H), 3.37 (d, 3-Heq, under reduced pressure. The oily product was triturated with
14.4 Hz, 1H), 3.96 (d, J = 14.8 Hz, 5-Ha, 1H), 4.12 (d, J = 14.8 ether to afford rac-trans-7a as yellow solid (131 mg, 96%) with
Hz, 5-Hb, 1H), 4.66 (d, J = 10.0 Hz, 2-H, 1H), 7.04 (m, 7-H, mp 262–264 °C. 1H NMR (400 MHz, CDCl3) δ 2.91 (s, N-Me,
8-H, 2H), 7.17 (m, 6-H, 9-H, 2H), 7.31–7.43 (m, Ph, 5H); 13C 3H), 3.12 (d, J = 16.8 Hz, 9-Ha, 1H), 3.13 (s, N-Me, 3H), 3.87
NMR (100 MHz, CDCl3) δ 52.5 (C-5), 58.9 (C-3), 86.4 (C-2), (dd, J = 16.4 and 12.0 Hz, 3-Hax, 1H), 4.00 (d, J = 16.8 Hz,
121.6 (C-9), 123.6 (C-7), 125.8 (C-2’, C-6’), 127.7 (C-8), 128.4 9-Hb, 1H), 4.16 (dd, J = 12.0 and 3.2 Hz, 3-Heq, 1H), 4.81 (s,
(C-3’, C-5’), 129.0 (C-4’, C-6), 135.6 (C-5a), 140.5 (C-1’), 15a-H, 1H), 5.13 (dd, J = 12.0 and 3.2 Hz, 2-H, 1H), 6.80 (d, J
159.1 (C-9a); IR (KBr) ν: 1579, 2935, 3328 cm−1; HRMS–ESI = 7.6 Hz, 19-H, 1H), 6.85 (d, J = 9.2 Hz, 5-H, 1H), 7.10 (m,
(m/z): [M + H]+ calcd for C15H16NO, 226.1232; found, 16-H, Ph, 3H), 7.15 (m, 17-H, 1H), 7.30–7.38 (m, 18-H, Ph,
226.1235; Anal. calcd for C15H15NO (225.11): C, 79.97; H, 4H), 8.08 (dd, J = 9.2 and 2.4 Hz, 6-H, 1H), 8.13 (s, 8-H, 1H);
6.71; N, 6.22; found: C, 80.03; H, 6.76; N, 6.18.
13C NMR (100 MHz, CDCl3) δ 28.7 (Me), 28.9 (Me), 34.7
(C-9), 47.3 (C-3) 51.9 (C-10), 71.5 (C-15a), 81.2 (C-2), 109.9
5-Nitro-2-(2-phenyl-2,3-dihydro-1,4-benzoxazepin-4(5H)- (C-19), 121.5 (C-15b), 123.8 (C-5), 124.7 (C-17), 124.8 (C-6),
yl)benzaldehyde (rac-5): To the stirred solution of rac-10 125.5 (C-8a), 127.0 (C-2’ and C-6’), 128.8 (C-3’ and C-5’),
(1.50 g, 6.66 mmol) in dry toluene (25 mL), anhydrous K2CO3 129.1 (C-8), 129.9 (C-18), 132.1 (C-16), 137.6 (C-7), 138.3
(1.85 g 13.39 mmol) and 2-fluoro-5-nitrobenzaldehyde (1.35 g, (C-1’), 147.6 (C-13), 150.1 (C-19a), 151.7 (C-4a), 167.1
7.98 mmol) were added and the mixture was refluxed for 8 h. (C-15), 168.9 (C-11); IR (KBr) ν: 749, 988, 1326, 1683, 2926
After cooling to room temperature, K2CO3 was filtered off and cm−1; HRMS–ESI (m/z): [M + Na]+ calcd for C28H24N4O6Na,
2600