3610
E. Brenner et al. / Tetrahedron Letters 45 (2004) 3607–3610
O.; Tamagnan, G.; Kimes, A. S.; Chambers, J.; Vaupel, D.
product was purified by flash chromatography on silica gel
with an eluent of EtOAc/hexane (3:7) to provide a white
solid (7.51 g, 84%): mp 162–164 °C; 1H NMR (CD3OD,
400 MHz) d 8.11–8.06 (m, 2H), 7.43–7.41 (m, 1H), 5.03 (s,
1H); 13C NMR (CD3OD, 100 MHz) d 156.8 (C), 142.3
(CH), 137.7 (CH), 127.3 (CH), 122.1 (C).
B.; King, S. L.; Picciotto, M. R.; Innis, R. B.; London, E.
D. Mol. Pharmacol. 2000, 57, 642–649; (d) Fujita, M.;
Tamagnan, G.; Zoghbi, S. S.; Al-Tikriti, M. S.; Baldwin,
R. M.; Seibyl, J. P.; Innis, R. B. J. Nucl. Med. 2000, 41,
1552–1560; (e) Fujita, M.; Tamagnan, G.; Zoghbi, S. S.;
Al-Tikriti, M. S.; Baldwin, R. M.; Seibyl, J. P.; Innis, R. B.
J. Nucl. Med. 2000, 41, 1552–1560; (f) Musachio, J. L.;
Scheffel, U. A.; Finley, P. A.; Zhan, Y.; Mochizuki, T.;
Wagner, H. N., Jr.; Dannals, R. F. Life Sci. 1998, 62, 351–
357.
13. Data for (S)-5-bromo-3-(1-benzyloxycarbonyl-2-azetidin-
20
ylmethoxy)pyridine (13): colorless oil; ½aꢀ ꢁ57.8 (c 1.31,
D
CHCl3); 1H NMR (CDCl3, 400 MHz) d 8.31–8.18 (m, 2H),
7.42–7.21 (m, 6H), 5.15–4.99 (m, 2H), 4.63–4.52 (m, 1H),
4.45–4.22 (m, 1H), 4.13–3.91 (m, 3H), 2.46–2.25 (m, 2H);
13C NMR (CDCl3, 100 MHz) d 156.1 (C), 155.2 (C), 143.2
(CH), 136.5 (CH), 136.4 (C), 128.5 (CH), 128.1 (CH),
127.9 (CH), 124.0 (CH), 120.3 (C), 68.6 (CH2), 66.6 (CH2),
60.1 (CH), 47.3 (CH2), 19.2 (CH2). Anal. Calcd for
C17H17BrN2O3: C, 54.13; H, 4.54; N, 7.43. Found: C,
53.87; H, 4.56; N, 7.31.
5. (a) Musachio, J. L.; Villemagne, V. L.; Scheffel, U. A.;
Dannals, R. F.; Dogan, A. S.; Yokoi, F.; Wong, D. F.
Nucl. Med. Biol. 1999, 26, 201–207; (b) Horti, A. G.;
Koren, A. O.; Lee, K. S.; Mukhin, A. G.; Vaupel, D. B.;
Kimes, A. S.; Stratton, M.; London, E. D. Nucl. Med.
Biol. 1999, 26, 175–182.
6. (a) Lynch, J. K.; Holladay, M. W.; Ryther, K. B.; Bai, H.;
Hsiao, C.-N.; Morton, H. E.; Dickman, D. A.; Arnold,
W.; King, S. A. Tetrahedron: Asymmetry 1998, 9, 2791–
2794; (b) Wentrup, C.; Winter, H.-W. J. Am. Chem. Soc.
1980, 102, 6161–6163; (c) Zervas, L.; Winitz, M.; Green-
stein, J. P. J. Org. Chem. 1957, 22, 1515.
7. (a) Krapcho, J.; Turk, C.; Cushman, D. W.; Powell, J. R.;
DeForrest, J. M.; Spitzmiller, E. R.; Karanewsky, D. S.;
Duggan, M.; Rovnvak, G.; Schwartz, J.; Natarajan, S.;
Godfrey, J. D.; Ryono, D. E.; Neubeck, R.; Atwal, K. S.;
Petrillo, E. W., Jr. J. Med. Chem. 1988, 31, 1148–1160; (b)
Ben-Ishai, D.; Berger, A. J. Org. Chem. 1952, 17, 1564–
1570.
14. Data for (S)-5-trimethylstannyl-3-(1-benzyloxycarbonyl-
20
2-azetidinylmethoxy)pyridine (14): colorless oil; ½aꢀ
D
ꢁ54.8 (c 1.36, CHCl3); 1H NMR (CD2Cl2, 500 MHz) d
8.25 (s, 2H), 7.43–7.29 (m, 6H), 5.16–5.07 (m, 2H), 4.68–
4.63 (m, 1H), 4.47–4.30 (m, 1H), 4.20–4.16 (m, 1H), 4.05–
3.97 (m, 2H), 2.47–2.37 (m, 2H), 0.39 (s, 9H); 13C NMR
(CD2Cl2, 125 MHz) d 156.9 (C), 155.7 (C), 148.7 (CH),
138.4 (C), 138.1 (CH), 137.7 (C), 129.2 (CH), 128.7 (CH),
128.5 (CH), 69.2 (CH2), 67.1 (CH2), 61.2 (CH), 48.2
(CH2), 20.1 (CH2),ꢁ8.9 (CH3). HRMS (EI) calcd for
C20H26N2O3Sn: 458.0972, found 458.0960.
15. Li, Z.; Ding, Y.-S.; Gifford, A.; Fowler, J. S.; Gatley, J. S.
Bioconjug. Chem. 2003, 14, 287–294.
8. (a) Celimene, C.; Dhimane, H.; Lhommet, G. Tetrahedron
1998, 54, 10457–10468; (b) Bajwa, J. S. Tetrahedron Lett.
1992, 33, 2299–2302; (c) Felix, A. M.; Heimer, E. P.;
Lambros, T. J.; Tzougraki, C.; Meienhofer, J. J. Org.
Chem. 1978, 43, 4194–4196.
9. Corey, E. J.; Shibata, S.; Bakshi, R. K. J. Org. Chem.
1988, 53, 2861–2863.
10. Abreo, M. A.; Lin, N.-H.; Garvey, D. S.; Gunn, D. E.;
Hettinger, A.-M.; Wasicak, J. T.; Pavlik, P. A.; Martin, Y.
C.; Donnelly-Roberts, D. L.; Anderson, D. J.; Sullivan, J.
P.; Williams, M.; Arneric, S. P.; Holladay, M. W. J. Med.
16. Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225–
2277.
17. (a) Heck, M. P.; Monthiller, S.; Mioskowski, C.; Guidot,
J. P.; Le Gall, T. Tetrahedron Lett. 1994, 35, 5445–5448; (b)
Jefferies, I. Bioorg. Med. Chem. Lett. 1992, 2, 1519–1522;
(c) Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870–
876; (d) Petter, R. C. Tetrahedron Lett. 1989, 30, 399–402;
(e) Ihara, M.; Taniguchi, N.; Noguchi, K.; Fukumoto, K.;
Kametani, T. J. Chem. Soc., Perkin. Trans. 1 1998, 1277–
1281; (f) Lott, R. S.; Chauhan, V. S.; Stammer, C. H.
J. Chem. Soc., Chem. Commun. 1979, 495–496.
Chem. 1996, 39, 817–825. (R)-1-(Benzyloxycarbonyl)-2-
18. Typical procedure for the preparation of (S)-5-trimethyl-
20
D
azetidinemethanol: lit.9 ½aꢀ þ15.5 (c 1.2, CHCl3); (S)-1-
stannyl-3-(2-azetidinylmethoxy)pyridine
(4 equiv, 3 ꢂ 0:077 mL, 3 ꢂ 1:33 equiv) were added in three
times every 30 min to solution of 14 (188 mg,
(4).
Me3SiI
20
(Benzyloxycarbonyl)-2-azetidinemethanol (7): ½aꢀ ꢁ17.0
D
(c 1.2, CHCl3).
11. Ziegler, F. E.; Bennett, G. B. J. Am. Chem. Soc. 1973, 95,
7458–7464.
a
0.407 mmol) in CH3CN (9 mL) at ꢁ5 °C. After 1.5 h
MeOH (6 equiv) was added and then the solution stirred
during 10 more minutes after which the solvent was
evaporated under reduced pressure and the crude product
purified by flash chromatography on silica gel with an
eluent MeOH/EtOAc (2:8) to provide a pale yellow solid
(123 mg, 92%): mp 52–54 °C; 1H NMR (CD3OD,
400 MHz) d 8.22 (s, 1H), 8.14 (s, 1H), 7.61 (s, 1H), 4.91–
4.79 (m, 1H), 4.43–4.38 (m, 2H), 4.13–3.97 (m, 2H), 2.65–
2.58 (m, 2H), 0.32 (s, 9H); 13C NMR (CD3OD, 100 MHz)
d 156.4 (C), 149.0 (CH), 140.7 (C), 138.4 (CH), 131.2
(CH), 69.0 (CH2), 60.9 (CH), 45.3 (CH2), 22.5 (CH2), ꢁ9.1
(CH3). HRMS (EI) calcd for C12H20N2OSn: 329.0657,
found 329.0674.
12. Typical procedure for the preparation of 3-bromo-5-
hydroxypyridine (11): 3-bromo-5-methoxypyridine (10)
(9.67 g, 51.4 mmol) was dissolved in 100 mL of CH2Cl2
and at 0 °C was added BBr3 (155 mL, 1 M in CH2Cl2,
3 equiv). The solution was stirred at room temperature for
2 days, then MeOH (70 mL) was slowly added and the
solvent was evaporated. MeOH (100 mL) was added and
the mixture was refluxed for 2 h and the solvent was
evaporated. Water was added and the pH adjusted to 7–8
with Na2CO3 before extracting the mixture three times
with EtOAc. The extracts were combined, dried, and the
solvent was evaporated under reduced pressure. The crude