5ꢀTrifluoromethyloxazolidineꢀ2,4ꢀdiones
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
1021
7.38 (d, 2 H, CHAr, J = 8.9 Hz); 7.50 (d, 2 H, CHAr, J = 8.9 Hz).
19F NMR (CDCl3), : 3.05 (d, J = 6.2 Hz).
Experimental
3ꢀBenzylꢀ5ꢀtrifluoromethyloxazolidineꢀ2,4ꢀdione (4d) was
obtained similarly to 4a from 1a (1.58 g, 0.01 mol) and benzyl
isocyanate (2c) (1.33 g, 0.01 mol). The yield was 2.2 g (85%),
m.p. 59—61 C. Found (%): C, 50.77; H, 3.29; N, 5.19.
C11H8F3NO3. Calculated (%): C, 50.98; H, 3.11; N, 5.40.
1H NMR (CDCl3), : 4.73 (s, 2 H, CH2); 5.03 (quartet, 1 H,
CH, J = 6.6 Hz); 7.37 (m, 5 H, CHAr). 19F NMR (CDCl3),
: 2.88 (d, J = 6.5 Hz).
5ꢀEthylꢀ3ꢀphenylꢀ5ꢀtrifluoromethyloxazolidineꢀ2,4ꢀdione (4e)
was obtained similarly to 4a from 1b (1.86 g, 0.01 mol) and
phenyl isocyanate (2b) (1.19 g, 0.01 mol). The yield was 2.1 g
(77%), m.p. 70—72 C. Found (%): C, 52.53; H, 3.51; N, 5.34.
C11H8F3NO3. Calculated (%): C, 52.75; H, 3.69; N, 5.13.
1H NMR (CDCl3), : 1.12 (t, 3 H, Me, J = 7.7 Hz); 2.32 (septet,
2 H, CH2, J = 7.7 Hz); 7.36—7.46 (m, 2 H, CHAr); 7.48—7.58
(m, 3 H, CHAr). 19F NMR (CDCl3), : 0.29 s.
1
H and 19F NMR spectra were recorded on a Bruker DPX
200 spectrometer (200.13 and 188.29 MHz), using Me4Si as an
internal standard and CF3COOH as an internal reference. Meltꢀ
ing point was determined in a capillary tube. Methyl 3,3,3ꢀtriꢀ
fluoroꢀ2ꢀhydroxypropionate (1a) was synthesized according to
the known procedure.5 Isocyanates 2a—d (Aldrich) were used as
purchased.
Methyl 2ꢀhydroxyꢀ2ꢀtrifluoromethylbutanoate (1b). Ethylꢀ
magnesium bromide (13.3 g) in THF (100 mL) was added to
a solution of methyl trifluoropyruvate (5) (15.6 g, 0.1 mol) in
THF (100 mL) at –30 C with stirring. The reaction mixture was
stirred for 1 h at 20 C, then poured into saturated aqueous NaCl
(300 mL), the organic layer was separated, the solvent was
evaporated, the residue fractionally distilled. The yield was 13.6 g
(73%), b.p. 40—43 C (10 Torr). Found (%): C, 38.53; H, 4.66.
C6H9F3O3. Calculated (%): C, 38.72; H, 4.87. 1H NMR (CDCl3),
: 0.87 (t, 3 H, Me, J = 7.1 Hz); 1.87 (m, 2 H, CH2); 3.72 (s, 3 H,
MeO); 3.78 (s, 1 H, OH). 19F NMR (CDCl3), : –1.05 s.
3ꢀPropylꢀ5ꢀtrifluoromethyloxazolidineꢀ2,4ꢀdione (4a). Triꢀ
ethylamine (0.1 g) was added to a solution of methyl 3,3,3ꢀtriꢀ
fluoroꢀ2ꢀhydroxypropionate (1a) (1.58 g, 0.01 mol) and propyl
isocyanate (2a) (0.85 g, 0.01 mol) in MeCN (10 mL) at 20 C
with stirring. After the exothermic reaction was over, the reacꢀ
tion mixture was refluxed for 10 min, the solvent was evaporatꢀ
ed, the residue was subjected to chromatography on silica gel
(eluent methanol—chloroform, 1 : 20). The yield was 1.77 g
(81%), oil. Found (%): C, 39.63; H, 4.06; N, 6.47. C7H8F3NO3.
Calculated (%): C, 39.82; H, 3.82; N, 6.63. 1H NMR (CDCl3),
: 0.95 (t, 3 H, Me, J = 7.3 Hz); 1.72 (sextet, 2 H, CH2, J = 7.4 Hz);
3.60 (td, 2 H, CH2, Jt = 7.3 Hz, Jd = 1.5 Hz); 5.12 (quartet, 1 H,
CH, J = 6.6 Hz). 19F NMR (CDCl3), : 5.19 (d, J = 6.8 Hz).
3ꢀPhenylꢀ5ꢀtrifluoromethyloxazolidineꢀ2,4ꢀdione (4b) was
obtained similarly to 4a from 1a (1.58 g, 0.01 mol) and phenyl
isocyanate (2b) (1.19 g, 0.01 mol). The yield was 1.9 g (78%),
m.p. 70—72 C. Found (%): C, 49.21; H, 2.28; N, 5.53. C10H6NO3.
Calculated (%): C, 48.99; H, 2.47; N, 5.71. 1H NMR (CDCl3),
: 5.20 (quartet, 1 H, CH, J = 6.5 Hz); 7.35—7.46 (m, 2 H,
CHAr); 7.48—7.57 (m, 2 H, CHAr). 19F NMR (CDCl3), : 2.94 s
(d, J = 6.3 Hz).
This work was financially supported by the Russian
Academy of Sciences (Program of the Division of Chemꢀ
istry and Material Sciences of the RAS "Medicinal and
Biomedicinal Chemistry) and the Russian Foundation for
Basic Research (Project Nos 11ꢀ03ꢀ00496ꢀa and 12ꢀ03ꢀ
00828ꢀa).
References
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3ꢀ(4ꢀChlorophenyl)ꢀ5ꢀtrifluoromethyloxazolidineꢀ2,4ꢀdione
(4c) was obtained similarly to 4a from 1a (1.58 g, 0.01 mol) and
4ꢀchlorophenyl isocyanate (2c) (1.54 g, 0.01 mol). The yield was
2.2 g (79%). M.p. 91—93 C. Found (%)): C, 42.72; H, 2.28;
N, 5.22. C10H5ClF3NO3. Calculated (%): C, 42.96; H, 2.47;
N, 5.01. 1H NMR (CDCl3), : 5.21 (quartet, 1 H, CH, J = 6.4 Hz);
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Received December 24, 2012;
in revised form February 21, 2013