1824
RAGULIN
of 1,2-dibromoethane was added in one portion, and
the mixture was stirred for 5 h at 120 C. The formed
trimethylbromosilane and excess 1,2-dibromoethane
were removed in a vacuum, and 50 ml of aqueous
ethanol (1 : 1) was added dropwise to the residue.
The mixture was refluxed for 0.5 h, and the solvent
NMR spectrum (D O + DCl), , ppm: 1.70 m
2
(2H), 1.88 m (4H), 2.36 d.t (2H, J 12 Hz), 3.92 t
HP
(1H). 13C NMR spectrum (D O), C, ppm: 26.4 d
2
(P CH C, J 91.4 Hz), 27.3 d (P CH C, J 90.2 Hz),
2
2
28.9 d (C CH CH, J 2.4 Hz), 31.4 d [C CH C(O),
2
2
J 3.1 Hz], 57.5 d (CH, J 15.8 Hz), 183.3 d [C(O)CH ,
2
was evaporated in a vacuum. The residue was treated J 17.1 Hz), 183.6 s [C(O)CH]. 31P NMR spectrum:
with 100 ml of ethyl acetate and 50 ml of water, and
the aqueous layer was extracted with ethyl acetate C 34.06, 33.93; H 6.07, 6.08; N 5.89, 5.86.
50 ml). The combined organic layers were evapo-
C H NO P 0.5H O. Calculated, %: C 33.88; H 6.09,
50.0 (D O), 44.0 (D O + NaOD, pH 10). Found, %:
P
2 2
(2
7
14
6
2
rated in a vacuum, the residue was treated with 40 ml
of triethyl orthoformate, and the mixture was refluxed
with a Dean Stark trap to remove ethanol and ethyl
formate. Excess triethyl orthoformate was removed in
a vacuum, and the residue was distilled to give 4.2 g
N 5.64.
The H, 13C, and 31P NMR spectra were recorded
on a Bruker DPX-200 Fourier spectrometer relative
to internal TMS and external 85% phosphoric acid.
1
(
1
(
40%) of vinylphosphinate II as an oil with bp 125
TLC analysis was performed on glass plates
(Merck), eluent 1-butanol acetic acid water (5 : 1 : 1).
2
0
1
29 C/3 mm Hg, n 1.4600. H NMR spectrum
D
CDCl ), , ppm: 1.25 t (3H, CH ), 1.34 t (3H, CH ),
3 3 3
2
.07 m (2H, PCH ), 2.60 m [2H, C(O)CH ], 4.03 m
2 2
ACKNOWLEDGMENTS
(
(
2H, CH OC), 4.15 m (2H, CH OP), 6.00 6.50 m
3H, CH=CH2).
2
2
3
1
P NMR spectrum (CDCl3):
P
The work was supported by Nippon Chemical
Industrial Co. [11].
4
1.3 ppm. Found, %: C 49.14, 49.33; H 7.97, 8.11.
C H O P. Calculated, %: C 49.09; H 7.78.
9
17
4
REFERENCES
2
-(Hydroxycarbonyl)ethyl-3-amino-3-(hydroxy-
carbonyl)propylphosphinic acid I. A mixture of 6.8 g
of diethyl acetamidomalonate, 7.5 g of vinylphos-
phinate II, 8.6 g of potassium carbonate, and 0.5 g
of tetrabutylammonium bromide in 20 ml of THF was
refluxed with stirring for 11 13 h until diethyl acet-
amidomalonate was completely consumed (TLC mon-
itoring, elution with (4 5) : 1 chloroform acetone,
1
2
. Collinsova, M. and Jiracek, J., Curr. Med. Chem.,
000, vol. 7, no. 6, pp. 629 647.
. Chen, H., Noble, F., Mothe, A., Meudal, H., Coric, P.,
Danascimento, S., Roques, B.P., George, P., and
Fournie-Zaluski, M.-C., J. Med. Chem., 2000, vol. 43,
no. 7, pp. 1398 1408.
2
3
. Burchardt, J., Ferreras, M., Krog-Jensen, C., Delais-
se, J.-M., Fored, N.T., and Meldal, N., Chem. Eur. J.,
1999, vol. 5, no. 10, pp. 2877 2884.
Rf 0.5 (Silufol). The reaction mixture was treated
with 50 ml of chloroform and 25 ml of water, and the
aqueous phase was neutralized and treated with chlo-
4
5
. Ragulin, V.V. and Tsvetkov, E.N., Izv. Akad. Nauk
SSSR, Ser. Khim., 1988, no. 11, p. 2652.
. Kurdyumova, N.R., Rozhko, L.F., Ragulin, V.V., and
Tsvetkov, E.N., Zh. Obshch. Khim., 1997, vol. 67,
no. 12, pp. 1970 1973.
roform (2
were evaporated in a vacuum. The oily residue (about
4 g) was treated with 70 ml of 8 N HCl, and the
25 ml). The combined organic extracts
1
mixture was refluxed for 13 15 h. Then the reaction
mixture was cooled and washed with diethyl ether
6. Voronkov, M.G. and Marmur, L.Z., Zh. Obshch.
Khim., 1970, vol. 40, no. 9, pp. 2135 2136.
(3
20 ml), the solvent was evaporated in a vacuum,
and the residue was chromatographed on a Dowex
7. Issleib, K., Mogelin, W., and Balszuweit, A., Z. Anorg.
Allg. Chem., 1985, vol. 530, no. 1, pp. 16 21.
+
50W(H ) column, elution with 0.5 0.7 N HCl. The
fractions with the positive ninhydrin test were concen-
trated, dissolved in 20 ml of aqueous ethanol (1 : 4),
and treated with an excess of propylene oxide to iso-
late the target amino acid. After the additional crystal-
lization of the product from aqueous ethanol, 5.3 g
of I was obtained (71% based on diethyl acetamido-
malonate). Total yield 28% based on ammonium hypo-
8
. Kurdyumova, N.R., Rozhko, L.F., Ragulin, V.V., and
Tsvetkov, E.N., Zh. Obshch. Khim., 1997, vol. 67,
no. 12, pp. 1965 1969.
9. Kurdyumova, N.R., Ragulin, V.V., and Tsvetkov, E.N.,
Zh. Obshch. Khim., 1996, vol. 66, no. 5, pp. 769 771.
10. Kurdyumova, N.R., Ragulin, V.V., and Tsvetkov, E.N.,
Mendeleev Commun., 1997, no. 2, pp. 69 70.
1
phosphite; mp 205 207 C with decomposition. H
11. JPN Patent B2000-18568, January 27, 2000.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001