(93 mg, 0.32 mmol), and the reaction mixture was stirred at
room temperature for 1 h. The reaction mixture was diluted with
AcOEt. The organic layer was washed by water and brine, dried
over Na2SO4, and concentrated under reduced pressure. The
resulting residue was purified by silica gel column chromato-
graphy (AcOEt–n-hexane = 1 : 1) to give 4a (138 mg, 91%) as a
white solid: mp 132–133 °C; IR νmax/cm−1 (KBr) 1703, 1523,
1461, 1427, 1341, 1233, 1125, 1097; 1H NMR (400 MHz;
CDCl3) δ 3.32–3.35 (2H, m), 3.47 (1H, ddd, J = 3.0, 14.5, 18.0
Hz), 3.65 (1H, ddd, J = 5.0, 14.0 Hz), 3.85–3.98 (3H, m),
4.62–4.82 (2H, m), 5.50–5.57 (2H, m), 7.36–7.63 (8H, m), 7.77
(2H, dd, J = 4.5, 8.0 Hz), 7.92 (1H, d, J = 8.0 Hz), 8.08 (1H, d,
J = 8.0 Hz), 8.19 (1H, s); 13C NMR (75 MHz; DMSO-d6,
80 °C) δ 41.54, 41.65, 49.35, 51.15, 62.81, 69.66, 69.90,
119.04, 119.64, 124.07, 125.10, 127.72, 128.44, 128.65, 128.78,
130.04, 131.48, 133.31, 135.72, 138.44, 147.02, 147.27, 154.20;
Mass (FAB) m/z 528 (M + H+); HRMS (FAB) calcd for
C28H26N5O6: 528.1883. Found: 528.1895; Anal. Calcd for
C28H25N5O6: C, 63.75; H, 4.78; N, 13.28. Found: C, 63.81; H,
4.86; N, 13.22.
74%) as a pale yellow foam: IR νmax/cm−1 (KBr) 1704, 1580,
1522, 1459, 1433, 1362, 1328, 1278, 1247, 1220, 1123, 1093,
1
1067, 1037; H NMR (400 MHz; CDCl3) δ 3.30–3.33 (2H, m),
3.57 (1H, dd, J = 5.0, 13.0 Hz), 3.59 (1H, d, J = 5.0 Hz), 3.91
(6H, s), 3.92–4.07 (3H, m), 4.62–4.81 (2H, m), 5.42–5.64 (2H,
m), 6.94 (1H, s), 7.37–7.40 (1H, m), 7.42–7.51 (4H, m),
7.71–7.76 (3H, m), 7.93 (2H, d, J = 8.0 Hz), 8.22 (1H, s); 13C
NMR (75 MHz; DMSO-d6, 90 °C) δ 41.59, 41.74, 49.32, 51.23,
55.87, 55.91, 62.99, 69.66, 69.85, 99.65, 108.41, 111.02,
118.91, 119.55, 125.07, 126.50, 127.65, 128.37, 130.02, 135.70,
138.36, 139.54, 146.98, 147.81, 153.07, 154.27; Mass (FAB) m/
z 588 (M + H+); HRMS (FAB) calcd for C30H30N5O8:
588.2094. Found: 588.2097.
(3RS,4RS,5RS)-3,4-Epoxy-N-(1-(2-nitrophenyl)ethoxycarbonyl)-
5-[4-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyloxy]piperidine (4d)
To a solution of 3 (100 mg, 0.29 mmol) and triethylamine
(44 mg, 60 μL, 0.44 mmol) in CH2Cl2 (3.0 mL) was added 2d
(88 mg, 0.29 mmol), and the reaction mixture was stirred at
room temperature for 10 min. The reaction mixture was diluted
with AcOEt. The organic layer was washed by water and brine,
dried over Na2SO4, and concentrated under reduced pressure.
The resulting mixture was purified by silica gel column chrom-
atography (AcOEt–n-hexane = 1 : 1) to give a diastereomixture
of 4d (150 mg, 97%) as a white foam: IR νmax/cm−1 (KBr)
1698, 1523, 1458, 1425, 1354, 1248, 1125, 1091, 1039; 1H
NMR (400 MHz; CDCl3) δ 1.65–1.67 (3H, m), 3.32–3.87 (4H,
m), 3.96–3.98 (2H, m), 4.52–4.89 (2H, m), 6.19–6.29 (1H, s),
7.33–7.92 (10H, m), 7.86–7.96 (3H, m), 8.17–8.22 (1H, m);
Mass (FAB) m/z 542 (M + H+); HRMS (FAB) calcd for
C29H28N5O6: 542.2040. Found: 542.2047.
(3RS,4RS,5RS)-N-(3,5-Dimethoxybenzyloxycarbonyl-3,4-epoxy)-
5-[4-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyloxy]piperidine (4b)
To a solution of 3 (50 mg, 0.14 mmol) and triethylamine
(22 mg, 30 μL, 0.22 mmol) in CH2Cl2 (1.5 mL) was added 2b
(49 mg, 0.16 mmol), and the reaction mixture was stirred at
room temperature for 30 min. The reaction mixture was diluted
with AcOEt. The organic layer was washed by water and brine,
dried over Na2SO4, and concentrated under reduced pressure.
The resulting mixture was purified by silica gel column chrom-
atography (AcOEt–n-hexane = 1 : 1) to give 4b (58 mg, 74%) as
a white solid: mp 73–77 °C; IR νmax/cm−1 (KBr) 1698, 1598,
1521, 1459, 1424, 1360, 1322, 1281, 1234, 1205, 1154, 1125,
1092, 1070, 1038; 1H NMR (400 MHz; CDCl3) δ 3.28–3.33
(2H, m), 3.46 (1H, dd, J = 3.0, 14.0 Hz), 3.63 (1H, dd, J = 5.0,
14.0 Hz), 3.75 (3H, s), 3.78 (3H, s), 3.85–3.98 (3H, m),
4.61–4.85 (2H, m), 5.05–5.01 (2H, m), 6.41 (1H, s), 6.50 (2H,
s), 7.36–7.54 (5H, m), 7.72 (1H, d, J = 8.0 Hz), 7.77 (1H, d, J =
8.0 Hz), 7.92 (2H, d, J = 8.0 Hz), 8.20 (1H, s); 13C NMR
(75 MHz; DMSO-d6, 80 °C) δ 41.54, 41.60, 49.38, 51.21,
54.83, 65.88, 69.65, 69.93, 99.40, 105.08, 119.04, 119.65,
125.10, 127.72, 128.45, 130.05, 135.72, 138.45, 138.81, 147.03,
154.65, 160.31; Mass (FAB) m/z 543 (M + H+); HRMS (FAB)
calcd for C30H31N4O6: 543.2244. Found: 543.2225.
N-2-Nitrobenzyloxycarbonylpiperidine (5a)
To a solution of piperidine (100 mg, 1.17 mmol) in CH2Cl2
(5 mL) was added triethylamine (177 mg, 0.24 mL, 1.76 mmol)
and 2a (300 mg, 1.17 mmol) at rt. The reaction mixture was
stirred for 15 min at room temperature, diluted with Et2O, and
washed with water and brine. The organic layer was dried over
MgSO4 and concentrated under reduced pressure. The resulting
residue was purified by silica gel column chromatography
(AcOEt–n-hexane = 1 : 2) to give 5a (250 mg, 72%) as a yellow
oil; IR νmax/cm−1 (KBr): 2983, 2857, 1702, 1527, 1469, 1433,
1343, 1283, 1147, 1092, 1076, 1026; 1H NMR (400 MHz;
CDCl3) δ 1.54–164 (6H, m), 3.46 (4H, brs), 5.53 (2H, s), 7.47
(1H, dt, J = 1.5, 8.0 Hz), 7.56 (1H, dd, J = 1.0, 8.0 Hz), 7.64
(1H, dt, J = 1.5, 8.0 Hz), 8.07 (1H, dd, J = 1.0, 8.0 Hz); 13C
NMR (75 MHz; DMSO-d6, 80 °C) δ 23.3, 24.8, 44.1, 62.5,
124.0, 128.5, 128.8, 131.8, 133.2, 147.4, 153.6; Mass (FAB) m/z
265 (M + H+); HRMS (FAB) calcd for C13H17N2O4: 265.1188.
Found: 265.1194.
(3RS,4RS,5RS)-N-(4,5-Dimethoxy-2-nitrobenzyloxycarbonyl)-
3,4-epoxy-5-[4-(4-phenyl-1H-1,2,3-triazol-1-yl)benzyloxy]-
piperidine (4c)
To a solution of 3 (50 mg, 0.14 mmol) and triethylamine
(22 mg, 30 μL, 0.22 mmol) in CH2Cl2 (1.5 mL) was added 2c
(56 mg, 0.16 mmol), and the reaction mixture was stirred at
room temperature for 30 min. The reaction mixture was diluted
with AcOEt. The organic layer was washed by water and brine,
dried over Na2SO4, and concentrated under reduced pressure.
The resulting mixture was purified by silica gel column
chromatography (AcOEt–n-hexane = 1 : 1) to give 4c (62 mg,
N-1-(2-Nitrophenyl)ethoxycarbonyl piperidine (5b)
To a solution of piperidine (100 mg, 1.17 mmol) in CH2Cl2
(5 mL) was added triethylamine (177 mg, 0.24 mL, 1.76 mmol)
and 2d (360 mg, 1.17 mmol) at rt. The reaction mixture was
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5102–5108 | 5107