Z. Guo et al. / Tetrahedron Letters 42 (2001) 1843–1845
1845
Scheme 4.
Scheme 5.
In conclusion, we have developed a novel method for
the selective monoamidation of diesters with primary or
secondary amines mediated by Lewis acids under mild
conditions. This simple procedure provides the corre-
sponding amides in excellent yields. A variety of amines
and esters with differing steric and electronic properties
are tolerated under these conditions.
Y.; Starreet, J. E.; Weinreb, S. M. J. Org. Chem. 1981, 46,
5383.
5. (a) Hanzlik, R. P. Inorganic Aspects of Biological and
Organic Chemistry; Academic Press: New York, 1976; p.
215; (b) Comins, D.; Meyers, A. I. Synthesis 1978, 403; (c)
Eiki, T.; Horiguchi, T.; Ono, M.; Kawada, S.; Tagaki, W.
J. Am. Chem. Soc. 1982, 104, 1986; (d) Hanessian, S.;
Kagotani, M.; Komaglou, K. Heterocycles 1989, 28, 1115;
(e) Sammakia, T.; Jacobs, J. S. Tetrahedron Lett. 1999, 40,
2685.
Acknowledgements
6. Typical experimental procedure: A 250 mL flask was
charged with dimethyl pyridine-2,5-dicarboxylate 1 (5.0 g,
25.6 mmol), MgCl2 (0.5 equiv., 1.22 g, 12.8 mmol), and
THF (100 mL) at room temperature. The slurry obtained
was stirred for 5 min, followed by the addition of CH3NH2
(2 M in THF, 25.6 mL) dropwise over 10 min. Stirring was
continued for 1.5 h at room temperature. The reaction was
monitored by HPLC for the disappearance of the starting
material 1. H2O (50 mL) and aqueous HCl solution (1N,
26 mL) were added to the reaction mixture. The resulting
mixture was then extracted with EtOAc (3×150 mL). The
combined organic phases were washed with brine (50 mL)
and dried over anhydrous MgSO4. The mixture was then
filtered and the solvent removed under reduced pressure to
give 4.78 g of 3b in 96% yield with HPLC AP 99 as a white
solid (Shimadzu LC-10AC; YMC ODS-AQ, 4.6×150 mm,
S-5 micron column; Shimadzu SPD-M10A spectrophoto-
metric detector at u=240 nm; eluent A: 0.1% HOAc in
H2O and eluent B: 0.1% HOAc in CH3CN). 1H NMR (400
MHz, CDCl3): l 3.05 (d, J=5.2 Hz, 3H), 3.97 (s, 3H), 8.05
(s, 1H), 8.28 (d, J=8.7 Hz, 1H), 8.44 (dd, J=2.0, 2.0 Hz,
1H), 9.12 (d, J=1.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3): l 26.9, 53.1, 121.6, 127.8, 138.4, 149.0, 152.5,
163.5, 164.7. MS m/z (M+1): 195.
The authors express their gratitude to the Analytical
Research and Development Department, Bristol-Myers
Squibb Pharmaceutical Research Institute at New
Brunswick for the NMR and LC-MS spectra.
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No attempt was made to examine SnCl2 for other com-
pounds since MgCl2 worked well.
.
.