M. Lo´pez et al. / Il Farmaco 55 (2000) 40–46
45
a clear yellow solid. TLC (FM B) 0.35; m.p. 143–
144°C; H NMR l (ppm) 3.70 (3H, s, CH3), 4.75 (2H,
ethyl esters, as side chain, were synthesized. Yields were
higher than those described in Method B. This proce-
dure could be useful for obtaining other similar com-
pounds in the alkoxyimino groups that contain
functional groups sensitive to the alkaline hydrolysis
and that cannot usually be prepared by traditional
Method A.
1
s, OCH2R), 6.80 (1H, s, aminothiazole), 7.03 (1H, s,
CH(C6H5)2), 7.3–7.5 (12H, m, (C6H5)2 +NH2); 13C
NMR l (ppm) 51.73 (CH3), 70.91 (OCH2R), 78.34
(CH(C6H5)2), 109.90 (C-5 aminothiazole), 140.54 (C-4
aminothiazole), 147.27 (CꢀNꢁOR), 161.28 (*COOCH-
(C6H5)2), 168.89 (C-2 aminothiazole), 169.32 (*COO-
CH3).
Acknowledgements
3.7. Diphenylmethyl-(Z)-2-(2-formamido-4-thiazolyl)-
2-(methoxycarbonylmethoxy imino) acetate (L5)
This work was partly supported by the Funds of the
University of Bologna, Italy.
A mixture of acetic anhydride (4 ml, 42.3 mmol) and
formic acid 99% (1.6 ml, 42.4 mmol) was stirred at
40°C for 1 h. To the mixture was added L4 (4.5 g; 10.59
mmol) and the reaction mixture was stirred at r.t. for 3
h. The obtained solution was stirred with n-hexane (15
ml) and ethyl acetate (15 ml). The resulting precipitate
was collected by filtration, washed with n-hexane and
dried at 40°C in a stove to afford 3.7 g (77.1%) of L5.
References
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1
TLC (FM B) 0.45; m.p. 143–144°C; H NMR l (ppm)
3.70 (3H, s, CH3), 4.80 (2H, s, OCH2R), 7.05 (1H, s,
CH(C6H5)2), 7.3–7.5 (12H, m, (C6H5)2 +NH2), 8.5
(1H, s, HCO), 12.60 (1H, s, NH); 13C NMR l (ppm)
51.77 (CH3), 71.10 (OCH2R), 78.57 (CH(C6H5)2),
115.94 (C-5 aminothiazole), 139.50 (C-4 aminothia-
zole), 146.85 (CꢀNꢁOR), 157.32 (C-2 aminothiazole),
160.14 (CHO), 160.98 (*COOCH), 169.20 (*COOCH3).
3.8. (Z)-2-(2-Formamido-4-thiazolyl)-
2-(methoxycarbonylmethoxyimino)acetic acid (L6)
To a solution of L5 (3.5 g 7.73 mmol) in 10 ml of
dichloromethane were added anisole (4.8 ml, 43.94
mmol) and trifluoroacetic acid (14 ml, 182.93 mmol)
under ice cooling. After 30 min at the same tempera-
ture, the mixture was poured into isopropyl ether. The
resulting solid was collected by filtration, washed with
isopropyl ether and dried at 40°C in stove to give 1.9 g
(85.7%) of L6. TLC (FM A) 0.58; m.p. 159–160°C (d);
1H NMR l (ppm) 3.68 (3H, s, CH3), 4.78 (2H, s,
OCH2R), 7.55 (1H, s, aminothiazole), 8.52 (1H, s,
HCO), 12.63 (1H, s, NH); 13C NMR l (ppm) 51.69
(CH3), 70.87 (OCH2R), 115.42 (C-5 aminothiazole),
140.12 (C-4 aminothiazole), 148.12 (CꢀNꢁOR), 157.08
(C-2 aminothiazole), 160.05 (CHO), 163.13 (COOH),
169.37 (*COOCH3).
4. Conclusions
A method for the synthesis of (Z)-2-(2-formamido-4-
thiazolyl)-2-(substituted alkoxyimino) acetic acids (I)
was developed by means of which derivatives of this
type, containing alkoxyimino substituted by methyl or
[11] R. Bucourt, R. Heyme´s, J. Perronet, A. Lutz, L. Pe´nasse,
Influence de la substitution de l’oxime sur l’activite´ antibacte´ri-
enne dans la se´rie du ce´fotaxime, Eur. J. Med. Chem. 16 (1981)
307–316.