40:1 v/v) to yield 8.6 g of 13 (92%) as a white solid (mp 145~146°C). [α]D24 +33.4° (c 0.54, CHCl3); IR
(KBr) cm-1: 3300, 1640, 1510, 1250; 1H-NMR (CDCl3) δ: 7.29-7.45 (m, 5H), 7.09 (ddd, J=6.6, 8.6, 11.5
Hz, 2H), 6.93 (ddd, J=6.6, 8.6, 11.5 Hz, 2H), 5.05 (s, 2H), 3.47 (s, 2H), 3.29-3.41 (m, 1H), 3.04 (s, 3H),
13
2.84-3.02 (m, 4H), 1.55 (br s, 1H); C-NMR δ: 33.3, 36.4, 45.2, 49.9, 60.3, 69.9, 115.1, 127.4, 127.9,
128.5, 129.8, 130.1, 136.8, 157.6, 168.4; Anal. Calcd for C19H22N2O2: C, 73.52; H, 7.14; N, 9.03. Found:
C, 73.39; H, 7.27; N 8.93.
(6S)-6-(4-Hydroxybenzyl)-1-methylpiperazin-2-one (14): To a stirred solution of 13 (4.0 g, 12.9 mmol)
in MeOH (70 mL) was added 10% Pd on carbon (400 mg, 10% based on 13), and the mixture was
allowed to stir for 2 h at rt under H2 atmosphere. The reaction mixture was filtered through a pad of Celite.
The filtrate was concentrated under reduced pressure and residual mixture was purified by silica gel
column chromatography (CH2Cl2:MeOH, 6:1 v/v) to yield 2.7 g of 14 (96%) as a white solid (mp
24
1
206.5~207.8°C). [α]D +45.7° (c 0.95, EtOH); IR (KBr) cm-1: 3120, 2950, 2320, 1620, 1510; H-NMR
(CD3OD) δ: 7.06 (ddd, J=6.4, 8.4, 11.4 Hz, 2H), 6.74 (ddd, J=6.4, 8.4, 11.4 Hz, 2H), 3.46 (ddd, J=5.8, 9.4,
13.5 Hz, 1H), 3.35 (s, 2H), 3.31 (quint, J=1.6 Hz, 1H), 3.04 (dd, J=4.3, 13.5 Hz, 1H), 3.00 (s, 3H),
13
2.76-2.91 (m, 3H); C-NMR δ: 33.9, 37.1, 45.3, 49.7, 61.4, 116.5, 129.5, 131.4, 157.4, 170.8; MS m/z
calcd for C12H17N2O2 (M+): 221.1302. Found: 221.1290; Anal. Calcd for C12H16N2O2: C, 65.43; H, 7.32;
N, 12.72. Found: C, 65.20; H, 7.43; N, 12.49.
(5S)-Spiro{4-methyl-1,4-diazabicyclo[3.2.1]octan-3-one-7,1’-cyclohexa-2’,5’-dien-4’-one} (15): To a
solution of iodobenzene diacetate (1.10 g, 3.42 mmol) in 1,1,1,3,3,3-hexafluoro-2-propanol (40 mL) was
added dropwise a solution of 14 (0.70 g, 3.18 mmol) in 1,1,1,3,3,3-hexafluoro-2-propanol (5 mL) at 0°C
and the resulting mixture was allowed to stir for 1 h at the same temperature. After removal of volatiles,
the residual mixture was purified by silica gel column chromatography (CH2Cl2:MeOH, 25:1 v/v) to yield
0.48 g of 15 (69%) as a white solid (mp 124.5~126.2°C). [α]D20 -23.52° (c 0.53, CHCl3); IR (KBr) cm-1:
1
2970, 1670, 1630; H-NMR (CDCl3) δ: 6.82-6.76 (m, 2H), 6.29 and 6.14 (each distorted d, J=9.7 Hz,
each 1H), 3.93 (dd, J=4.1, 2.8 Hz, 1H), 3.75 (d, J=18.5 Hz, 1H), 3.58 (dd, J=18.5, 1.5 Hz, 1H), 3.46 (dd,
J=12.7, 3.0 Hz, 1H), 3.20 (br d, J=12.7 Hz, 1H), 3.00 (s, 3H), 2.30 (dd, J=13.8, 2.8 Hz, 1H), 2.11 (dd,