6
Tetrahedron
ACCEPTED MANUSCRIPT
(t, J = 4.6 Hz, 4H), 3.09 (t, J = 4.8 Hz, 4H); 13C NMR (100
Wang, T.-C.; Tzeng, C.-C. J. Med. Chem. 2000, 43, 3809–3812; (e)
1
3
Kulkarni, P. M.; Kulkarni, A. R.; Korde, A.; Tichkule, R. B.;
Laprairie, R. B.; Denovan-Wright, E. M.; Zhou, H.; Janero, D. R.;
Zvonok, N.; Makriyannis, A.; Cascio, M. G.; Pertwee, R. G.; Thakur,
G. A. J. Med. Chem. 2016, 59, 44–60.
MHz, CDCl3) δ 155.7 (d, JCF = 244.5 Hz), 140.0 (d, JCF = 8.4
Hz), 139.3, 124.5 (d, JCF = 3.6 Hz), 122.7 (d, JCF = 7.9 Hz),
118.7 (d, JCF = 2.9 Hz), 116.2 (d, JCF = 20.6 Hz), 114.1, 67.0,
51.0, 50.9; 19F NMR (376 MHz, CDCl3) δ –122.9 to –123.0 (m,
1F).
4
3
4
2
2. (a) Ramgren, S. D.; Silberstein, A. L.; Yang, Y.; Garg, N. K. Angew.
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5475.
4.2.29. 4-(2- and 3-Methoxyphenyl)morpholine (3ne, CAS:
27347-13-3: CAS: 32040-09-8).2a Yellow liquid. Yield 64%. H
1
NMR (400 MHz, CDCl3) δ 7.17 (t, J = 8.0 Hz, 0.29 × 1H, m-
isomer), 7.02–6.97 (m, 0.71 × 1H, o-isomer), 6.92 (d, J = 4.0 Hz,
0.71 × 2H, o-isomer), 6.86 (d, J = 8.0 Hz, 0.71 × 1H, o-isomer),
6.52–6.50 (m, 0.29 × 1H, m-isomer), 6.44–6.41 (m, 0.29 × 2H,
m-isomer), 3.87 (t, J = 4.6 Hz, 0.71 × 4H, o-isomer), 3.84 (s, 0.71
× 3H, o-isomer), 3.82 (t, J = 5.0 Hz, 0.29 × 4H, m-isomer), 3.75
(s, 0.29 × 3H, m-isomer), 3.12 (t, J = 4.8 Hz, 0.29 × 4H, m-
isomer), 3.05 (t, J = 4.6 Hz, 0.71 × 4H, o-isomer); 13C NMR (100
MHz, CDCl3) δ 160.7, 152.7, 152.3, 141.2, 129.9, 123.2, 121.1,
118.0, 111.4, 108.5, 104.7, 102.2, 67.2, 66.9, 55.4, 55.2, 51.2,
49.3.
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338.
4.2.30. 1-(2,5-Dimethoxyphenyl)-2,2,6,6-tetramethylpiperidine
1
(3gm). White crystal. Mp 77.2–77.7 °C. Yield 78%. H NMR
(400 MHz, CDCl3) δ 6.90 (d, J = 3.2 Hz, 1H), 6.76 (d, J = 8.8
Hz, 1H), 6.72–6.69 (m, 1H), 3.76 (s, 3H), 3.71 (s, 3H), 1.86–1.80
(m, 1H), 1.62–1.51 (m, 5H), 1.24 (s, 6H), 0.80 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 154.8, 152.4, 136.7, 121.1, 110.8, 110.0,
55.6, 55.4, 54.3, 41.7, 31.4, 25.8, 18.5; HRMS (EI) calcd for
C17H27NO2 [M]+ 277.2042, found 277.2043.
4.2.31. 4-(2,5-Dimethoxyphenyl)morpholine (3ge, CAS: 154519-
06-9).6a Yellow liquid. Yield 83%. 1H NMR (400 MHz, CDCl3) δ
6.77 (d, J = 8.8 Hz, 1H), 6.53 (d, J = 2.4 Hz, 1H), 6.49ꢀdd, J =
8.6, 3.0 Hz, 1Hꢁ, 3.87 (t, J = 4.6 Hz, 4H), 3.81 (s, 3H), 3.76 (s,
3H), 3.06 (t, J = 4.4 Hz, 4H); 13C NMR (100 MHz, CDCl3) δ
154.2, 146.6, 142.2, 112.1, 106.1, 105.5, 67.1, 55.9, 55.6, 51.0.
4.2.32. N,N-Dibutyl-2,5-dimethoxyaniline (3gj, CAS: 84311-83-
1
1).6a Yellow liquid. Yield 45%. H NMR (400 MHz, CDCl3) δ
6.76 (d, J = 8.8 Hz, 1H), 6.54 (d, J = 2.8 Hz, 1H), 6.44 (dd, J =
8.8, 2.8 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.08 (t, J = 7.6 Hz,
4H), 1.48–1.41 (m, 4H), 1.30–1.24 (m, 4H), 0.88 (t, J = 7.4 Hz,
6H); 13C NMR (100 MHz, CDCl3) δ 153.9, 148.0, 141.4, 112.8,
108.7, 104.7, 56.2, 55.5, 52.4, 29.1, 20.6, 14.0.
4.2.33. 1-Phenyl-4-(pyridin-2-yl)piperazine (3mh, CAS: 682773-
1
53-1).2a Yellow solid. Mp 108.3–109.5°C. Yield 92%. H NMR
(400 MHz, CDCl3) δ 8.21 (dd, J = 4.8, 1.6 Hz, 1H), 7.51–7.46
(m, 1H), 7.28 (dd, J = 8.6, 7.4 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H),
6.88 (t, J = 7.4 Hz, 1H), 6.68 (d, J = 8.8 Hz, 1H), 6.64 (dd, J =
7.2 Hz, 5.2 Hz, 1H), 3.69 (t, J = 5.2 Hz, 4H), 3.29 (t, J = 5.2 Hz,
4H); 13C NMR (100 MHz, CDCl3) δ 159.5, 151.3, 148.0, 137.6,
129.2, 120.1, 116.4, 113.6, 107.3, 49.2, 45.3.
Acknowledgments
12. Zhu, F.; Wang, Z-X. Adv. Synth. Catal. 2013, 355, 3694–3702.
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Financial support from the National Natural Science
Foundation of China (Grant Nos. 21472043 and 21302128) is
gratefully acknowledged.
References and notes
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