R
SYNTHETIC COMMUNICATIONSV
5
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1
lit.[9f] [a]D ¼ þ177 (c ¼ 1.0, MeOH). H NMR (400 MHz, CDCl3): d ¼ 2.32 ꢀ 2.48 (m,
2H), 3.38 (br s, N-1H), 3.48 (d, J ¼ 17.2 Hz, 1H), 3.63 (d, J ¼ 17.1 Hz, 1H), 4.00 (dd,
J ¼ 14.3, 4.4 Hz, 1H), 5.78 ꢀ 5.81 (m, 1H), 5.89 ꢀ 5.93 (m, 1H), 7.27 (dd, J ¼ 7.8, 2.4 Hz,
1H), 7.83 (d, J ¼ 7.9 Hz, 1H), 8.52 (d, J ¼ 1.9 Hz, 1H), 8.66 (s, 1H) ppm. 13C NMR
(100 MHz, CDCl3): d ¼ 32.4, 44.9, 55.0, 123.7, 124.4, 125.2, 134.7, 137.3, 148.8,
149.3 ppm. IR (CHCl3): ꢀmax ¼ 3401, 3020, 2973, 1661, 1523, 1475, 1426, 1092, 1047,
928, 670 cmꢀ1. HRMS (ESI–TOF) m/z: [M þ Na]þ calcd. for C10H12N2Na 183.0893,
found 183.0894. A similar procedure was used for the TFA based reaction of compound
10e to give 3a in 70% yield.
(R)-3-(Piperidin-2-yl)pyridine, (R)-anabasine (4a)
To a solution of 3a (15 mg, 0.094 mmol) in dry EtOH (3 mL), Pd/C (4 mg, 10% Pd on C)
was added and the reaction mixture was stirred under H2 (balloon pressure) for 12 h at
room temperature. The reaction mixture was filtered through a small pad of Celite and the
pad washed with CH2Cl2 (2 ꢁ 10 mL). The filtrate was concentrated under vacuo and the
residue was purified by silica gel column chromatography using CH2Cl2/MeOH (4:1) as
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eluent to give (R)-anabasine 4a (11.5 mg, 76%) as pale brown oil. [a]D ¼ þ56.3 (c ¼ 0.58,
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MeOH), lit.[9f] [a]D
¼ þ80.2 (c ¼ 1.0, MeOH). 1H NMR (400 MHz, CDCl3):
d ¼ 1.50 ꢀ 1.59 (m, 1H), 1.63 ꢀ 1.75 (m, 3H), 1.82 ꢀ 1.96 (m, 2H), 2.79 ꢀ 2.86 (m, 1H),
3.20 (d, J ¼ 11.8 Hz, 1H), 3.72 (dd, J ¼ 11.3, 2.6 Hz, 1H), 7.25 (t, J ¼ 2.0 Hz, 1H), 7.81 (d,
J ¼ 7.9 Hz, 1H), 8.49 (d, J ¼ 2.2 Hz, 1H), 8.61 (d, J ¼ 2.0 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3): d ¼ 24.4, 24.5, 33.3, 46.9, 59.4, 123.6, 134.7, 138.2, 148.7, 149.0 ppm. IR
(CHCl3): ꢀmax ¼ 3020, 2939, 2862, 1683, 1515, 1462, 1155, 1086, 1034, 669 cmꢀ1. HRMS
(ESI–TOF) m/z: [M þ Na]þ calcd. for C10H14N2Na 185.1049, found 185.1048.
Funding
This work was supported by Council of Scientific and Industrial Research (CSIR), New Delhi,
India [02(0158)/13/EMR-II]. J.L.N. thank CSIR for a research fellowship.
ORCID
Rodney A. Fernandes
References
[1] (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.; Whitter,
W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; et al. Methods for
Drug Discovery: Development of Potent, Selective, Orally Effective Cholecystokinin
A. D.; Molyneux, R. Alkaloids; Chemical and Biological Perspectives; John Wiley & Sons:
New York, NY, 1987; pp 1. (c) Sardina, F. J.; Rapoport, H. Enantiospecific Synthesis of
Heterocycles from a-Amino Acids. Chem. Rev. 1996, 96, 1825–1872. DOI: 10.1021/
cr9300348. For reviews on 5- and 6-membered N-heterocyclic top marketing drug mole-
cules, see; (d) Baumann, M.; Baxendale, I. R.; Ley, S. V.; Nikbin, N. An Overview of the