J = 7.8, H-2ꢅ, 6ꢅ), 7.06 (2H, d, J = 7.8, H-3ꢅ, 5ꢅ), 7.89 (1H, dd, J = 7.8 and 8.2, H-5ꢀ), 8.14 (1H, dd, J = 8.2 and 1.2, H-4ꢀ), 8.80
(1H, d, J = 7.8, H-6ꢀ), 9.08 (1H, d, J = 1.2, H-2ꢀ).
(S)-3-{1-[2-(2,6-Dimethoxyphenoxy)ethyl]piperidin-2-yl}pyridine (16b) oxalate, light oil, yield 0.58 g (39%),
[ꢂ] –142.1° (c 0.5, EtOH). PMR spectrum [(CD ) CO, ꢁ, ppm, J/Hz]: 1.40 (1H, m, H-4), 1.50 (1H, m, H-3), 1.55–1.66 (3H,
D
3 2
m, H-3, 5, 5), 1.75 (1H, m, H-4), 2.28–2.40 [2H, m, H-6, 1H-(CH N)], 2.75 [1H, m, 1H-(CH N)], 3.33 (1H, m, H-6), 3.73 (6H,
2
2
s, 2 ꢃ OCH ), 3.89 (2H, m, CH O), 4.38 (1H, dd, J = 11.2 and 2.2, H-2), 6.58 (2H, br.d, J = 7.4, H-3ꢅ, 5ꢅ), 6.92 (1H, t, J = 7.4,
3
2
H-4ꢅ), 7.31 (1H, ddd, J = 8.0, 8.2, and 1.2, H-5ꢀ), 7.78 (1H, ddd, J = 8.2 and 1.2, H-4ꢀ), 8.45 (1H, dd, J = 8.0 and 1.2, H-6ꢀ), 8.56
13
(1H, dd, J = 1.2 and 1.2, H-2ꢀ). C NMR spectrum (CDCl , ꢁ, ppm): 25.5 (C-4), 26.7 (C-5), 37.6 (C-3), 54.7 (CH N), 55.3
3
2
(C-6), 56.3 (2 ꢃ OCH ), 66.4 (C-2), 71.1 (CH O), 105.8 (C-3ꢅ, 5ꢅ), 124.2, 124.4 (C-4ꢅ, 5ꢀ), 135.9 (C-4ꢀ), 138.3 (C-1ꢅ), 141.4
3
2
(C-3ꢀ), 148.8 (C-6ꢀ), 149.9 (C-2ꢀ), 154.5 (C-2ꢅ, 6ꢅ). Mass spectrum (m/z, I , %): 341 (1.1), 189 (45), 175 (100), 117 (17), 92
rel
+
(17), 65 (9). Found: [M – H] 341.1849; C H N O ; calcd: 342.1938.
20 25
2 3
(S)-3-{1-[3-(2,6-Dimethoxyphenoxy)propyl]piperidin-2-yl}pyridine (17b) oxalate, oil, yield 0.57 g (37%),
[ꢂ] –108.6° (c 0.4, EtOH). PMR spectrum [(CD ) CO, ꢁ, ppm, J/Hz]: 1.64–2.46 (8H, m, CH and H-3, 3, 4, 4, 5, 5), 2.68–
D
3 2
2
2.88 [1H, m, 1H-(CH N)], 3.05 [1H, m, 1H-(CH N)], 3.33 (1H, m, H-6), 3.73 (6H, s, 2 ꢃ OCH ), 3.87 (2H, m, CH O), 3.92
2
2
3
2
(1H, m, J
= 11.8, H-6), 4.52 (1H, dd, J = 11.2 and 2.2, H-2), 6.58 (2H, br.d, J = 8.2, H-3ꢅ, 5ꢅ), 6.97 (1H, t, J = 8.2, H-4ꢅ),
gem
7.72 (1H, dd, J = 8.0 and 7.6, H-5ꢀ), 8.43 (1H, dd, J = 8.0 and 1.2, H-4ꢀ), 8.71 (1H, d, J = 7.6, H-6ꢀ), 8.92 (1H, d, J = 1.2, H-2ꢀ).
(S)-3-{1-[4-(2,6-Dimethoxyphenoxy)butyl]piperidin-2-yl}pyridine (18b) oxalate, light oil, yield 0.57 g (35%).
PMR spectrum (D O, ꢁ, ppm, J/Hz): 1.30–2.02 (6H, m, 2 ꢃ CH and H-3, 5), 2.32–2.48 (4H, m, H-3, 4, 4, 5), 2.74 (3H, m,
2
2
NCH and H-6), 3.91 (6H, s, 2 ꢃ CH O), 4.12 (2H, m, CH O), 4.10 (m, 1H, H-2), 6.73 (2H, d, J = 8.2, H-3ꢅ, 5ꢅ), 7.14 (1H, t,
2
3
2
J = 8.2, H-4ꢅ), 8.10 (1H, dd, J = 8.0 and 7.6, H-5ꢀ), 8.31 (1H, dd, J = 8.0 and 1.2, H-4ꢀ), 9.02 (1H, m, H-6ꢀ), 9.39 (1H, br.s, H-2ꢀ).
(S)-3-{1-[2-(4-Allyl-2-methoxyphenoxy)ethyl]piperidin-2-yl}pyridine (19b) oxalate, yield 0.57 g (37%), mp 106–
106.5°C. PMR spectrum (CD OD, ꢁ, ppm, J/Hz): 1.74–2.23 (6H, m, H-3, 3, 4, 4, 5, 5), 3.04–3.42 (5H, m, NCH , H-6), 3.53–
3
2
3.69 (2H, m, =CCH ), 3.91 (3H, s, OCH ), 4.04 (1H, br.d, J = 11.4, H-6), 4.25 (2H, m, CH O), 4.70 (1H, br.d, J = 12.0, H-2),
2
3
2
5.19 (1H, m, =CH), 5.97 (1H, m, =CH), 6.74 (1H, br.d, J = 7.7, H-6ꢅ), 6.85–6.93 (2H, m, H-3ꢅ, 5ꢅ), 7.66 (1H, dd, J = 7.8 and
7.6, H-5ꢀ), 8.25 (1H, br.d, J = 7.8, H-4ꢀ), 8.69 (1H, dd, J = 7.6 and 1.5, H-6ꢀ), 8.85 (1H, br.s, H-2ꢀ). Mass spectrum
+
+
(m/z, I , %): 352 [M] (2), 189 (15), 175 (100), 132 (20), 28 (29). Found: [M] 352.2146; C H N O ; calcd: 352.2145.
rel
22 28 2 2
(S)-3-{1-[4-(4-Allyl-2-methoxyphenoxy)butyl]piperidin-2-yl}pyridine (20b) oxalate, yield 0.68 g (44%), mp 122–
123.5°C. PMR spectrum (CD OD, ꢁ, ppm, J/Hz): 1.53–1.70 (2H, m, CH ), 1.75–2.36 (8H, m, CH and H-3, 3, 4, 4, 5, 5),
3
2
2
3.35–3.69 (5H, m, NCH , =CCH and H-6), 3.80 (3H, s, OCH ), 4.26 (2H, m, CH O), 4.54 (1H, br.d, J = 12.0, H-2), 5.22 (1H,
2
2
3
2
m, =CH), 6.13 (1H, m, =CH), 6.67 (1H, br.s, H-6ꢅ), 6.75 (1H, br.d, J = 7.1, H-3ꢅ), 6.95 (1H, d, J = 7.1, H-4ꢅ), 7.58 (1H, m,
+
H-5ꢀ), 8.20 (m, 1H, H-4ꢀ), 8.61 (1H, d, J = 6.8, H-6ꢀ), 8.83 (1H, br.s, H-2ꢀ). Mass spectrum (m/z, I , %): 380 [M] (0.5), 217
rel
+
(44), 175 (100), 132 (22), 92 (8), 44 (16). Found: [M] 380.2456; C H N O ; calcd: 380.2458.
24 32
2 2
(S)-3-(1-{4(E)-[2-Methoxy-(4-prop-1-enyl)phenoxy]ethyl}piperidin-2-yl)pyridine (21b) oxalate, light oil, yield
0.63 g (38%), [ꢂ] –56.4° (c 0.4, EtOH). PMR spectrum (CD OD, ꢁ, ppm, J/Hz): 1.75–2.36 (6H, m, H-3, 3, 4, 4, 5, 5), 1.87
D
3
(3H, d, J = 7.0, CH ), 3.35–3.62 (3H, m, NCH and H-6), 3.78 (3H, s, OCH ), 4.28 (2H, m, CH O), 4.55 (1H, br.d, J = 11.6,
3
2
3
2
H-6), 5.88 (1H, d, J = 14.8, CH=), 6.42 (1H, m, J = 14.8, ArCH=), 6.82 (1H, br.s, H-3ꢅ), 7.38 (1H, br.d, J = 7.1, H-6ꢅ), 7.46
(1H, d, J = 7.1, H-5ꢅ), 7.64 (1H, m, H-5ꢀ), 8.26 (1H, m, H-4ꢀ), 8.55 (1H, d, J = 6.8, H-6ꢀ), 8.78 (1H, br.s, H-2ꢀ).
(S)-3-{1-[2-(4-Acetyl-2-methoxyphenoxy)ethyl]piperidin-2-yl}pyridine (22b) oxalate, light oil, yield 0.63 g (41%),
[ꢂ] –122.1° (c 0.5, EtOH). PMR spectrum (CD OD, ꢁ, ppm, J/Hz): 1.76–2.39 (6H, m, H-3, 3, 4, 4, 5, 5), 2.59 (3H, s, CH ),
D
3
3
3.35–3.54 (3H, m, NCH and H-6), 3.98 (3H, s, OCH ), 4.03 (1H, br.d, J = 12.2, H-6), 4.41 (2H, m, CH O), 4.74 (1H, dd,
2
3
2
J = 12.0 and 2.2, H-2), 7.04 (1H, d, J = 8.1, H-5ꢅ), 7.59 (1H, d, J = 1.5, H-3ꢅ), 7.66 (1H, dd, J = 8.1 and 1.5, H-6ꢅ), 7.75 (1H,
dd, J = 8.0 and 7.8, H-5ꢀ), 8.43 (1H, br.d, J = 7.8, H-4ꢀ), 8.66 (1H, dd, J = 7.8 and 1.5, H-6ꢀ), 8.95 (1H, br.s, H-2ꢀ). Mass
+
+
spectrum (m/z, I , %): 354 [M] (0.7), 189 (2), 175 (100), 132 (12), 92 (3), 44 (4). Found: [M] 354.1929; C H N O ;
rel
21 26 2 3
calcd: 354.1925.
(S)-3-{1-[3-(4-Acetyl-2-methoxyphenoxy)propyl]piperidin-2-yl}pyridine (23b) oxalate, yield 0.57 g (36%),
mp 97.5–99.5°C. PMR spectrum (CD OD, ꢁ, ppm, J/Hz): 1.76–2.39 (8H, m, CH and H-3, 3, 4, 4, 5, 5), 2.52 (3H, s, CH ),
3
2
3
3.01–3.34 (3H, m, NCH and H-6), 3.78 (3H, s, OCH ), 3.84–4.08 (3H, m, CH O and H-6), 4.44 (1H, br.d, J = 12.0, H-2), 6.89
2
3
2
(1H, d, J = 8.1, H-5ꢅ), 7.47 (1H, br.s, H-3ꢅ), 7.52 (1H, m, H-6ꢅ), 7.58 (1H, br.d, J = 8.0, H-5ꢀ), 8.09 (1H, m, H-4ꢀ), 8.61 (1H,
d, J = 7.8, H-6ꢀ), 8.70 (1H, br.s, H-2ꢀ). Mass spectrum (m/z, I , %): 368 (3), 290 (14), 175 (100), 132 (13), 118 (3), 92 (5), 44
rel
+
(7). Found: [M] 368.2088; C H N O ; calcd: 368.2094.
22 28
2 3
299