1880
S.H. Lee et al. / Tetrahedron 69 (2013) 1877e1880
anhydrous Na2SO4, and concentrated in vacuo. The residue was
(m, 1H), 2.78 (s, 3H), 2.75e2.84 (m, 1H), 4.70 (t, J¼7.8 Hz, 1H),
4.89e4.92 (m,1H), 7.07e7.08 (m,1H), 7.11 (dd, J¼8.0, 2.2 Hz,1H), 7.35
(d, J¼2.2 Hz, 1H), 7.43e7.51 (m, 3H), 7.63e7.66 (m, 1H); 13C NMR
purified by column chromatography (n-hexane/EtOAc¼6:1) to
afford 0.153 g (0.371 mmol, 75% yield) of 7 a white solid. Rf¼0.30
(n-hexane/EtOAc¼5:1); ½a D25
ꢄ
þ41.1 (c 1.0, CHCl3); mp 103e108 C;
(125 MHz, CD3OD) d 31.4, 39.9, 49.4, 64.2, 127.0, 127.1, 129.0, 129.4,
ꢂ
IR (KBr)
n
3320, 3027, 1679, 1524, 1260, 1237, 1028, 754, 659 cmꢀ1
;
131.2, 132.0, 132.1, 132.2, 133.7, 138.3, 145.8, 148.7; LC/MS (ESI) m/z
1H NMR (300 MHz, CDCl3)
d
2.46 (t, J¼6.1 Hz, 2H), 4.46 (t, J¼6.9 Hz,
292.00 [MþH]þ, 293.99 [Mþ2þH]þ.
1H), 4.92e5.10 (m, 1H), 5.15 (s, 2H), 5.29e5.39 (m, 1H), 6.92
(dd, J¼8.0, 1.9 Hz, 1H), 7.02 (d, J¼5.7 Hz, 1H), 7.18 (s, 1H), 7.22e7.46
Acknowledgements
(m, 9H); 13C NMR (125 MHz, CDCl3)
d 29.7, 44.1, 48.1, 67.0, 124.8,
125.3, 127.1, 128.0, 128.2, 128.3, 128.6, 129.0, 129.7, 130.6, 132.6,
136.4, 144.8, 145.0, 156.0; LC/MS (ESI) m/z 412.02 [MþH]þ, 414.19
[Mþ2þH]þ; HRMS (EI) calcd for C23H19NO2Cl2 [M]þ 411.0793,
found 411.0799.
This work was supported by the National Research Foundation
of Korea (NRF-2011-0029199 and NRF-2012-002506) funded by the
Ministry of Education, Science and Technology.
Supplementary data
4.1.6. Benzyl (1R,3S)-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-
1-yl methylcarbamate (8). To a stirred solution of 7 (0.144 g,
0.393 mmol) in anhydrous THF (7 mL) and DMF (1.7 mL) were
added NaH (28 mg, 0.70 mmol, 60% in mineral oil) and MeI
(0.087 mL, 1.40 mmol) at 0 ꢂC under N2. The reaction mixture was
stirred at room temperature for 12 h. The resulting mixture was
quenched with H2O (20 mL) and extracted with EtOAc (100 mLꢃ2).
The organic layer was washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was purified by
column chromatography (n-hexane/EtOAc¼10:1) to afford 0.159 g
(0.373 mmol, 95% yield) of 8 as a colorless oil. Rf¼0.27 (n-hexane/
HPLC analysis data of compounds 4a and 4b and 1H NMR and 13
NMR copies of all compounds. Supplementary data related to this
C
References and notes
1. Bøgesø, K. P.; Arnt, J.; Frederiksen, K.; Hansen, H. O.; Hyttel, J.; Pedersen, H. J.
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3. Guillon, J.; Dallemagne, P.; Leger, J.-M.; Sopkova, J.; Bovy, P. R.; Jarry, C.; Rault, S.
Bioorg. Med. Chem. 2002, 10, 1043.
EtOAc¼6:1); ½a 2D5
ꢄ
þ76.0 (c 1.0, CHCl3); IR (neat)
n 2925, 2854, 1700,
ꢀ
1469, 1401, 1323, 1138, 1029, 760, 698 cmꢀ1
;
1H NMR (300 MHz,
4. Hyttel, K.; Larsen, J.-J. J. Neurochem. 1985, 44, 1615.
CDCl3)
d
2.32e2.55 (m, 4H), 2.66 (s, 3H), 4.49 (dd, J¼8.8, 5.3 Hz, 1H),
5. (a) Graul, A.; Castaner, J. Drugs Future 1998, 23, 903; (b) Sterling, J.; Veinberg, A.;
Lerner, D.; Goldenberg, W.; Levy, R.; Youdim, M.; Finberg, J. J. Neural Transm.
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6. Bøgesø, K. P.; Arnt, J.; Boeck, V.; Christensen, A. V.; Hyttel, J.; Jensen, K. G. J. Med.
Chem. 1988, 31, 2247.
5.21 (s, 2H), 5.87e6.19 (m, 1H), 6.89 (dd, J¼8.4, 1.9 Hz, 1H), 7.04
(d, J¼5.7 Hz,1H), 7.16 (s, 1H), 7.24e7.39 (m, 9H); 13C NMR (125 MHz,
CDCl3)
d 29.7, 39.1, 48.7, 60.2, 67.3, 124.9, 125.4, 127.0, 127.8, 127.9,
128.0, 128.5, 128.8, 129.5, 130.4, 130.6, 132.6, 136.8, 141.3, 145.2,
145.7, 156.7; LC/MS (ESI) m/z 426.07 [MþH]þ, 428.05 [Mþ2þH]þ;
HRMS (EI) calcd for C24H21NO2Cl2 [M]þ 425.0949, found 425.0954.
7. Koe, B. K. J. Pharmacol. Exp. Ther. 1976, 199, 649.
8. Mendelson, J. H.; Mello, N. K. N. Engl. J. Med. 1996, 334, 965.
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pharmacology 1992, 107, 186.
4.1.7. (1R,3S)-3-(3,4-Dichlorophenyl)-N-methyl-2,3-dihydro-1H-in-
den-1-amine (9). To a stirred solution of 8 (0.100 g, 0.235 mmol) in
CH2Cl2 (2 mL) and MeOH (8 mL) was added Raney Nickel (30 mg).
The reaction mixture was stirred for 6 h under H2 balloon at room
temperature. The resulting mixture was filtered through a Celite
pad and concentrated in vacuo. The residue was purified by
column chromatography (CH2Cl2/MeOH¼15:1) to afford 62 mg
(0.212 mmol, 90% yield) of 1 as a colorless oil. Rf¼0.29 (CH2Cl2/
11. For references on the total synthesis of racemic indatraline, see: (a) Bøgesø, K.
P.; Christensen, A. V.; Hyttel, J.; Liljefors, T. J. Med. Chem. 1985, 28, 1817; (b)
Froimowitz, M. F.; Wu, K.-M.; Moussa, A.; Haidar, R. M.; Jurayj, J.; George, C.;
Gardner, E. L. J. Med. Chem. 2000, 43, 4981; (c) Cossy, J.; Belotti, D.; Maguer, A.
Synlett 2003, 1515; (d) Walton, J. G. A.; Jones, D. C.; Kiuru, P.; Durie, A. J.;
Westwood, N. J.; Fairlamb, A. H. ChemMedChem 2011, 6, 321 For a reference on
the formal synthesis of racemic indatraline, see; (e) Pastre, J. C.; Correia, C. R. D.
Adv. Synth. Catal. 2009, 351, 1217.
12. For references on the asymmetric total synthesis of (þ)-indatraline, see: (a)
Davies, H. M. L.; Gregg, T. M. Tetrahedron Lett. 2002, 43, 4951; (b) Roesner, S.;
Casatejada, J. C.; Elford., T. G.; Sonawane, R. P.; Aggarwal, V. K. Org. Lett. 2011, 13,
5740 For references on the asymmetric formal synthesis of (þ)-indatraline, see;
(c) Davies, H. M. L.; Walji, A. M. Org. Lett. 2003, 5, 479; (d) Yoo, K.; Kim, H.; Yun,
J. Chem.eeEur. J. 2009, 15, 11134; (e) Taylor, J. G.; Correia, C. R. D. J. Org. Chem.
2011, 76, 857; (f) Wei, W.-T.; Yeh, J.-Y.; Kuo, T.-S.; Wu, H.-L. Chem.dEur. J. 2011,
17, 11405.
MeOH¼9:1); ½a 2D5
ꢄ
ꢀ17.9 (c 1.0, CHCl3) [lit.12e
½
a 2D3
ꢄ
ꢀ18.9 (c 1.1,
CHCl3)]; 1H NMR (300 MHz, CDCl3)
d 1.28 (br, 1H), 2.20e2.29
(m, 1H), 2.41e2.49 (m, 1H), 2.52 (s, 3H), 4.26 (dd, J¼6.9, 3.1 Hz, 1H),
4.51 (t, J¼7.6 Hz, 1H), 6.97 (dd, J¼8.0, 1.9 Hz, 2H), 7.22e7.30 (m, 3H),
7.36 (d, J¼8.0 Hz, 1H), 7.39e7.42 (m, 1H); 13C NMR (125 MHz, CDCl3)
13. (a) Silva, L. F., Jr.; Siqueira, F. A.; Pedrozo, E. C.; Vieira, F. Y. M.; Doriguetto, A. C.
Org. Lett. 2007, 9, 1433; (b) Kameyama, M.; Siqueira, F. A.; Garcia-Mijares, M.;
Silva, L. F., Jr.; Silva, M. T. A. Molecules 2011, 16, 9421.
d
34.3, 43.4, 48.5, 63.7, 124.7, 125.3, 127.2, 127.5, 128.3, 129.9, 130.3,
130.4, 132.4, 145.0, 145.5, 145.6; LC/MS (ESI) m/z 292.00 [MþH]þ,
293.99 [Mþ2þH]þ; HRMS (FAB) calcd for C16H16Cl2N [MþH]þ
292.0660, found 292.0649.
14. Nørager, N. G.; Lorentz-Petersen, L. L. R.; Lyngsø, L. O.; Kehler, J.; Juhl, K. Synlett
2011, 1753.
15. For a submitted for publication review, see: (a) Kim, I. S.; Jung, Y. H. Heterocycles
2011, 83, 2489 For recent examples, see; (b) Kim, I. S.; Li, Q. R.; Dong, G. R.; Kim,
Y. C.; Hong, Y. J.; Lee, M.; Chi, K.-W.; Oh, J. S.; Jung, Y. H. Eur. J. Org. Chem. 2010,
1569; (c) Dong, G. R.; Hong, S. M.; Kim, S. I.; Kim, I. S.; Jung, Y. H. Eur. J. Org.
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4.1.8. (þ)-Indatraline (1). To a stirred solution of indatraline free
amine (9) (30 mg, 0.103 mmol) in diethyl ether (0.5 mL) was added
a solution of 1 M HCl (0.5 mL) at room temperature. The reaction
mixture was stirred at room temperature for 2 h. The precipitate was
filtered and washed with diethyl ether. The resulting solid was dried
in vacuo to afford 33 mg (0.100 mmol, 97% yield) of (þ)-indatraline as
16. Lee, S. H.; Kim, I. S.; Li, Q. R.; Dong, G. R.; Jeong, L. S.; Jung, Y. H. J. Org. Chem.
2011, 76, 10011.
17. Rendy, R.; Zhang, Y.; McElrea, A.; Gomez, A.; Klumpp, D. A. J. Org. Chem. 2004,
69, 2340.
18. For a representative submitted for publication review, see Corey, E. J.; Helal, C.
Angew. Chem., Int. Ed. Engl. 1998, 37, 1986.
19. Salunkhe, A. M.; Burkhardt, E. R. Tetrahedron Lett. 1997, 38, 1523.
20. For a detailed reaction mechanism, see: Ref. 16.
a white solid. Rf¼0.35 (CH2Cl2/MeOH/NH4OH¼9:1:0.1); ½a D25
þ30.1
ꢄ
(c 1.0, MeOH); mp 182e184 ꢂC; IR (MeOH)
n 3359, 2946, 2833, 1451,
1406, 1032, 820, 630 cmꢀ1; 1H NMR (300 MHz, CD3OD)
d 2.46e2.57