Vol. 27, No. 7 (2015)
Synthesis of 3-(5H-Pyrazolyl)cyclobutanone Derivatives 2547
to proceed for another 15 h at 90 °C. The reaction mixture
was cooled to room temperature and water (20 mL) was added.
The mixture was stirred at 100 °C for 2 h.After cooling to room
temperature, the product was extracted from diluted aqueous
3 %. For these reasons, it is not suitable for large scale prepa-
ration. The second route is based on the materials commercially
available. Although the starting material is more expensive,
the reaction involves 4 steps. The total yield was up to 8.6 %.
This synthetic route not only saves the time but lowers the cost
for manufacture. In summary, both synthetic routes success-
fully provided a strategy for synthesis of pyrazole cyclobutanone
derivatives.
NaHCO
organic layer was dried with Na
3
solution with CH
2
Cl
2
(3 × 100 mL). The combined
SO , filtered and concentrated
2
4
to give a brown oil. Purification by flash chromatography (PE:
EtOAc = 1:1) gave target compound 1 (192 mg, 36 %) as a
yellow oil. C11
2
3
H
14
N
2
O
3
(222.24). HPLC-MS (ESI+): t
23 [M + H] . H NMR (400 MHz, DMSO-d ) δ 6.80 (s, 1H);
.78-3.83 (q, 2H); 3.76 (s, 3H); 3.75-3.73 (m, 1H); 3.56-3.48
R
= 3.22,
+
1
ACKNOWLEDGEMENTS
6
The authors acknowledge the Sundia Medi Tech., Company
Ltd. for generous support of this work.
(
m, 2H); 3.34-3.26 (m, 2H); 1.28 (t, 3H).
In Scheme-II, we tried to synthesize target compound 1
with another route. The commercially available methylene-
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1
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14
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pyrazole compound 1c as a pale yellow oil. Finally, the terminal
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RESULTS AND DISCUSSION
1
1
1
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Two synthetic routes were investigated, of which one is
construction of cyclobutanone and another is construction of
pyrazole ring. In the first route, the pyrazole ring is available
and the starting material is low-cost and can be obtained easily.
But this synthetic route is longer and the total yield is only
1
1