2102
R. Zhao et al. / Tetrahedron Letters 42 (2001) 2101–2102
boxylates as shown in Scheme 1. N-Alkyl, N-benzyl
and N-aryl 2-aminothiazole-5-carboxylates 4b–e were
all readily prepared in good to excellent yields.8
4. Noto, R.; Ciofalo, M.; Buccheri, F.; Werber, G.; Spinelli,
D. J. Chem. Soc., Perkin Trans. 2 1991, 349.
5. Kaye, P. T.; Meakins, G. D.; Smith, A. K.; Tirel, M. D. J.
Chem. Soc., Perkin Trans. 1 1983, 1677.
In summary, a new facile synthesis of 2-aminothiazole-
5-carboxylates has been developed. Compared to the
previous two-step syntheses, the new one-pot method
not only is manipulatively simpler, but also affords
higher overall yields (60–98% versus <25%). In addi-
tion, the new intermediate, a-formyl-a-bromoacetate
hemiacetal 2, is expected to be useful for the synthesis
of a variety of heterocycles other than 2-aminothiazole-
5-carboxylates 4.
6. Ethyl a-formyl-a-bromoacetate was prepared similarly by
formylation of ethyl bromoacetate in 26% yield, see:
Yoffe, S. T.; Petrovsky, P. V.; Goryunov, Y. I.; Yershova,
T. V.; Kabachnik, M. I. Tetrahedron 1972, 28, 2783.
7. Typical procedure: To a mixture of ethyl b-ethoxyacrylate
1 (144.2 g, 1.0 mol) in water (500 mL) and dioxane (500
mL) at −10°C was added NBS (195.7 g, 1.1 mol, 1.1
equiv.). The reaction mixture was stirred at rt for 1 h and
HPLC showed disappearance of 1. Thiourea 3a (76.0 g,
1.0 mol, 1.0 equiv.) was added and the reaction mixture
was heated to 80°C for 1 h. After cooling to rt, conc.
NH4OH (200 mL) was added. The resulting slurry was
stirred at rt for 10 min and filtered. The cake was washed
with water (3×500 mL) and dried to give 2-aminothiazole-
5-carboxylate 4a (155.1 g, 90% yield), mp 159°C, lit.2
156–158°C. The NMR spectrum data were consistent with
those reported for this compound.2
References
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l 7.72 (s, 1H), 6.72 (br s, 1H), 4.24 (q, J=7.1 Hz, 2H),
3.55 (m, 1H), 1.29 (t, J=7.1 Hz, 3H), 1.27 (d, J=6.3 Hz,
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Hz, 2H), 4.29 (q, J=7.1 Hz, 2H), 3.83 (s, 3H), 1.33 (t,
J=7.1 Hz, 3H).
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