N. Defacqz et al. / Tetrahedron Letters 44 (2003) 9111–9114
9113
After cleavage of the N-protecting group by treatment
with iodotrimethylsilane in dichloromethane, the com-
pounds were isolated in poor yields (30–50%), as
fumarate salts from diethyl ether.20 Biological evalua-
tion was performed by determining the affinity of the
compounds for the rat a2 adrenoreceptor, the rat sero-
tonine reuptake site and the rat adrenaline reuptake site
by competition with [3H] RX 821002, [3H] paroxetine
and [3H] nisoxetine respectively.3 No notable activity
was found.
H-5), 7.46 (1H, broad s, H-2). 13C NMR (125 MHz,
CDCl3); l 27.9, 45.6, 52.3, 68.7, 82.4, 149.5, 150.2, 170.8.
MS m/z (EI) 228, 169, 155, 127, 69.
1
12. Spectral data for 2: H NMR (500 MHz, CDCl3); l 1.51
(9H, s, (CH3)3C), 3.56 (5H, m, H-4, H-4% and CH2OH),
4.30 (1H, m, H-5), 7.56 (1H, broad s, H-2). Anal. calcd
for C9H16N2O3: C, 53.08; H, 8.05; N, 13.99; found: C,
53.22; H, 7.99; N, 13.67.
13. (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93,
2117–2188; (b) Knochel, P.; Perea, J. J. A.; Jones, P.
Tetrahedron 1998, 54, 8275–8319.
14. (a) Hanessian, S.; Ponpipom, M. M.; Lavalle´e, P. Carbo-
hydr. Res. 1972, 24, 45–56; (b) Ja¨ger, V.; Ha¨fele, B.
Synthesis 1987, 801–806.
Acknowledgements
15. (a) Mitsunobu, O. Synthesis 1981, 1–28; (b) Simon, C.;
Sandor, H.; Dor, M. J. Heterocycl. Chem. 1997, 34,
349–357; (c) Hughes, D. L. Org. React. 1992, 42, 335–
656.
This work was generously supported by l’Institut de
Recherches Servier (France) and the Fonds National de
la Recherche Scientifique (FNRS, Belgium). We thank
A. Dekoker-Malengreau and B. Clamot for technical
assistance. J.M.-B. is a senior research associate of the
FNRS.
16. General procedure: Triphenylphosphine (1.5 equiv.) dis-
solved in tetrahydrofuran (100 mg/mL) was cooled to
0°C. Diisopropyl azodicarboxylate (1.5 equiv.) was added
and the mixture was allowed to stir for 10 min before
adding compound 2 (1 equiv.) and phenol (1.5 equiv.) (or
amine derivative) dissolved in tetrahydrofuran (100 mg/
mL). The mixture was stirred at room temperature for 48
h. By adding a small amount of diisopropyl ether, after
solvent evaporation, triphenylphosphine oxide precipi-
tated. After filtration, the crude mixture was purified by
preparative MPLC (SiO2: 15–40 m; P=100–110 kg/cm2;
UV: 245 nm; CH2Cl2/i-PrOH, 98/2).
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1
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1
(9H, s, (CH3)3C), 3.72 (4H, m, H-4 and CH3O), 3.83 (1H,
dd, J=7.7, 4.6 Hz, H-4%), 4.73 (1H, dd, J=10.0, 7.8 Hz,