3
66
Y. Miyahara et al.
SHORT PAPER
FAB MS: m/z = 207.21 (MH+).
Acknowledgement
Treatment of 1c with excess HClO gave its mono HClO salt as
4
4
This work was supported in part by a Grant-in-Aid for COE Rese-
arch "Design and Control of Advanced Molecular Assembly Sy-
stems" (#08CE2005) and a Grant-in-Aid for scientific research (C)
(#11640539) from the Ministry of Education, Science, Sports, and
Culture, Japan.
colorless plates (EtOH/CH CN), mp: 108.0 109.5 °C.
3
Anal. Calcd for C H N O Cl: C, 50.90; H, 7.56; N, 9.13. Found:
13
23
2
4
C, 50.92; H, 7.58; N, 9.11.
3
,7-Bis(carbethoxy)-3,7-diazabicyclo[3.3.1]nonane (1d)
To a stirred suspension of NaI (27.46 g, 0.183 mol) and ethyl chlo-
References
roformate (17.5 mL, 0.183 mol) in dry CH CN (150 mL) was added
3
a solution of 1c (6.30 g, 0.0305 mol) in dry CH CN (20 mL) at r.t.
3
(
1) a) Bohlmann, F.; Ottawa, N.; Keller, R. Liebigs Ann. Chem.
954, 587, 162.
The mixture was refluxed for 8 h and, after cooling to r.t., filtered.
The filtrate was evaporated under reduced pressure and the residue
was taken in EtOAc, washed with aqueous NaOH, dried (Na SO ),
1
b) Bohlmann, F.; Ottawa, N. Chem. Ber. 1955, 88, 1828.
c) Stetter, H.; Hennig, H. Chem. Ber. 1955, 88, 789.
d) Stetter H.; Merten, R. Chem. Ber. 1957, 90, 868.
e) Galinovsky, F.; Langer, H. Monatsh. Chem. 1955, 86, 449.
f) Galinovsky, F.; Sparatore, F.; Langer, H. Monatsh. Chem.
1956, 87, 100.
2
4
and passed through a column of silica gel (hexane/EtOAc, 3:2) to
give 6.03 g (73%) of 1d as a colorless oil, which crystallized upon
standing, mp: 58 60 °C.
IR (neat): = 2979, 2914, 2862, 1692, 1456, 1433, 1380, 1345,
1
1
305, 1263, 1237, 877, 881, 834, 760 cm .
(2) Douglass, J. E.; Ratliff, T. J. Org. Chem. 1968, 33, 355.
Ruenitz, P. C.; Mokler, C. M. J. Med. Chem. 1977, 20, 1668.
(
1H NMR (400 MHz, CDCl3): = 4.29 (d, 2H, J = 13.1 Hz,
NCH C), 4.21 (d, 2H, J = 13.1 Hz, NCH C), 4.07, 4.06 (two over-
3) Ruenitz, P. C.; Smissman, E. E. J. Org. Chem. 1977, 42, 937.
Gallagher, D. J.; Wu, S.; Nikolic, N. A.; Beak, P. J. Org.
Chem. 1995, 60, 8148.
2
2
lapping q, 4H, J = 7.0 Hz, OCH C), 3.07 (d, 2H, J = 13.1 Hz,
2
NCH C), 3.01 (d, 2H, J = 13.1 Hz, NCH C), 1.83 (s, 2H, CCH C),
2
2
2
Garrison, G. L.; Berlin, K. D.; Scherlag, B. J.; Lazzara, R.;
Patterson, E.; Fazekas, T.; Sangiah, S.; Chen. C. -L.; Schubot,
F. D.; van der Helm, D. J. Med. Chem. 1996, 39, 2559.
1
.81 (s, 2H, bridgehead CH), 1.24 (t, 6H, J = 7.0 Hz, CH3).
1
3
C NMR (100 MHz, CDCl ): = 156.14 (C = O), 61.53 (OCH C),
3
2
4
1
8.80, 48.61 (NCH C), 31.48 (CCH C), 28.12 (bridgehead CH),
5.03 (CH3).
(4) Miyahara, Y.; Goto, K.; Inazu, T. Chem. Lett. 2000, 620.
(5) Hancock et al. have mentioned 2b as their target molecule for
its expected strong in-plane ligand fields: Hancock, R. D.;
Pattrick, G.; Wade, P. W.; Hosken, G. D. Pure Appl. Chem.
2
2
Anal. Calcd for C H N O : C, 57.76; H, 8.20; N, 10.36. Found: C,
5
FAB MS: m/z = 271.08 (MH+).
1
3
22
2
4
7.79; H, 8.20; N, 10.32.
1
993, 65, 473.
6) Galík, V.; Landa, S. Collect. Czech. Chem. Commun. 1973,
8, 1101.
(
3
3
,7-Diazabicyclo[3.3.1]nonane (1a)
(7) Ruenitz, P. C.; Smissman, E. E. J. Heterocycl. Chem. 1976,
13, 1111.
(8) Olofson, R. A.; Martz, J. T.; Senet, J. P.; Piteau, M.; Malfroot,
T. J. Org. Chem. 1984, 49, 2081.
A solution of 1d (5.52 g, 20.4 mmol) in EtOH (20 mL) and 10 N
KOH (80 mL) was refluxed for 12 h. After distilling off all the
EtOH present, the reaction mixture was refluxed for an additional
2
0 h. Then, the reflux condenser was replaced with a Dean Stark
(9) du Vigneaud, V.; Behrens, O. K. J. Biol. Chem. 1937, 117, 27.
(10) Moreau, B.; Lavielle, S.; Marquet, A. Tetrahedron Lett. 1977,
2591.
trap and, after addition of benzene, heating was continued until the
H O present was completely removed azeotropically. When cooled,
2
the reaction mixture was filtered through a Celite pad. The solvent
was evaporated and the residue was distilled at 175 178 °C / 27
Torr by means of a Kugelrohr apparatus to yield 2.55 g of 1a (99%,
Hawkins, J. M.; Lewis, T. A. J. Org. Chem. 1994, 59, 649.
(11) Garro-Helion, F.; Merzouk, A.; Guibe, F. J. Org. Chem. 1993,
58, 6109.
3
7% overall yield from 4) as crystalline semisolid.
Lemaire-Audoire, S.; Savignac, M.; Genêt, J. P.; Bernard,
J.-M. Tetrahedron Lett. 1995, 36, 1267.
Jaime-Figueroa, S.; Liu, Y.; Muchowski, J. M.; Putman, D. G.
The crystals were extremely hygroscopic and quickly deliquesced
in the air. Actually, first several papers did not report the mp of 1a.
Tetrahedron Lett. 1998, 39, 1313.
Noting that the mp of 1a was highly sensitive to the amount of H O
7
2
(
(
12) The instability of bispidinone has been noticed.
13) Kuthan, J.; Palecek, J.; Musil, L. Collect. Czech. Chem.
Commun. 1974, 39, 750.
absorbed, Galinovsky et al. first reported its mp, measured in a care-
1
f
fully sealed capillary, as 134 135 °C. Later, however, a mp as
high as 203 205 °C was reported for a sample obtained by sublima-
tion at 130 135 °C.13 In our hands, crystals of 1a, which sublimed
at approx. 150 °C/1 atm and immediately sealed in a capillary under
Ar, showed mp: 158 161 °C.
(
14) In the synthesis of 1,5-diphenylbispidine, use of KOH leads
exclusively to 1,5-bispidine-9-ol: Stetter, H.; Schäfer, J.;
Dieminger, K. Chem. Ber. 1958, 91, 598. Although the later
papers reporting N,N -dialkylbispidines used KOH without
trouble, in the present case the use of KOAc is preferred.
IR (neat): = 3300 (br), 2902, 2855, 2799, 2732, 1566, 1493, 1454,
1
1
350, 1318, 1288, 1252, 1201, 834, 760 cm . (Even a freshly dis-
(15) Smissman, E. E.; Ruenitz, P. C.; Weis, J. A. J. Org. Chem.
1975, 40, 251. However, the yield of 1e has been so low (~2%
overall yield) for the authors of the recent paper on its use as
a powerful ligand for Ni(0) that they made a special comment
of welcome for a more efficient synthesis: Haack, K. -J.;
Goddard, R.; Pörschke, K.-R. J. Am. Chem. Soc. 1997, 110,
tilled sample of 1a showed very small bands at 2362 and 1644
cm 1 due to the hydrate of 1a, which increased on standing in air.)
1
H NMR (400 MHz, C D ): = 2.95 (d, 4H, J = 11.6 Hz, NCH C),
6
6
2
2
.88 (d, 4H, J = 12.1 Hz, NCH C), 1.87 (br, 2H, NH), 1.60 (s, 2H,
2
bridgehead CH), 1.18 (s, 2H, CCH C). (Strongly basic 1a decom-
2
7992.
poses in CDCl with abstracting D.)
3
(
16) Tidwell, J. H.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116,
1
3
C NMR (100 MHz, C D ): = 53.09 (NCH C), 34.37 (CCH C),
11797.
6
6
2
2
3
0.20 (bridgehead CH).
(17) Miyahara, Y.; Goto, K.; Inazu, T. to be published.
FAB MS: m/z = 127.10 (MH+)
Article Identifier:
1
437-210X,E;2001,0,03,0364,0366,ftx,en;F05500SS.pdf
Synthesis 2001, No. 3, 364–366 ISSN 0039-7881 © Thieme Stuttgart · New York