Synthesis of (S)-2-[(dioctylphosphoryl)methylamino]propionic acid from trimethylsilyl 2-(trimethylsilylamino)propanoate

Full text of DOI:10.1134/S1070428013040234

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 4, p. 624. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © R.A. Cherkasov, A.R. Garifzyanov, S.A. Koshkin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 4, p. 639.
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COMMUNICATIONS
Dedicated to the 100th Anniversary of Corresponding Member
of the Russian Academy of Sciences A.A. Petrov
Synthesis of (S)-2-[(Dioctylphosphoryl)methylamino]propionic
Acid from Trimethylsilyl 2-(Trimethylsilylamino)propanoate
R. A. Cherkasov, A. R. Garifzyanov, and S. A. Koshkin
Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia
e-mail: rafael.cherkasov@ksu.ru
Received February 5, 2013
DOI: 10.1134/S1070428013040234
We previously showed [1] that the Kabachnik–
Fields reaction in the system dioctylphosphine oxide–
paraformaldehyde–amino acid leads to the formation
of the corresponding N-(dioctylphosphorylmethyl)-
substituted amino acid derivatives. In particular,
N-phosphorylmethyl derivatives of glycine, β-alanine,
and N-butylglycine were synthesized in this way.
Because of poor solubility of amino acids in organic
solvents, the reactions were carried out in acetonitrile
in the presence of the corresponding amino acid hydro-
chloride. We made an attempt to perform phosphoryla-
tion of (S)-α-alanine under similar conditions. How-
ever, the reaction in heterogeneous medium gave
a mixture of mono- and bisphosphorylation products.
With a view to improve the selectivity, the Kabachnik–
Fields reaction was carried out with dioctylphosphine
oxide, paraformaldehyde, and trimethylsilyl (S)-2-(tri-
methylsilylamino)propanoate prepared by heating of
(S)-α-alanine with excess hexamethyldisilazane over
a period of 72 h under reflux. Heating of the reactants
in boiling toluene in the presence of p-toluenesulfonic
acid (reaction time 3 h) afforded 96% (according to the
31P–{1H} NMR data) of silylated aminomethylphos-
phine oxide I. Silylamine I was treated with a hot 15%
aqueous solution of sodium hydroxide, and the subse-
quent neutralization of sodium salt II with 10% aque-
ous HCl gave target acid III.
(S)-2-{[(Dioctylphosphoryl)methyl](trimethyl-
silyl)amino}propionic acid (I). White amorphous sub-
1
stance. H NMR spectrum (CDCl3), δ, ppm: 0.21 s
3
[9H, Si(CH3)3], 0.86 d (3H, CH3, JHH = 9 Hz), 1.25–
2
1.90 m (34H, C8H17), 2.88 d.d (2H, CH2P, JHH = 4,
2JPH = 18 Hz), 3.27 q (1H, CH, 3JHH = 9 Hz). 31P–{1H}
NMR spectrum (PhMe): δP 51.2 ppm, s.
(S)-2-[(Dioctylphosphoryl)methylamino]pro-
pionic acid (III). White crystalline substance,
mp 132°C. 1H NMR spectrum (CDCl3), δ, ppm: 0.87 d
Me
(S)
O
P
3
(3H, CH3, JHH = 9 Hz), 1.25–1.90 m (34H, C8H17),
Me3Si
+ CH2O +
OSiMe3
C8H17
2
2
N
H
H
2.89 d.d (2H, CH2P, JHH = 4, JPH = 18 Hz), 3.27 q
C8H17
(1H, CH, JHH = 9 Hz). 31P–{1H} NMR spectrum
3
O
O
P
C8H17
SiMe3
N
O
(CH2Cl2): δP 52.4 ppm, s.
TsOH
The H and 31P–{1H} NMR spectra were recorded
1
C8H17
C8H17
C8H17
–Me3SiOH
OH
on a Varian XL-300 spectrometer at 300 and
122.4 MHz, respectively.
Me
(S)-I
O
P
C8H17
O
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 13-03-00536).
NaOH
H
N
–Me3SiOH
ONa
OH
Me
Me
(S)-II
REFERENCE
O
P
C8H17
O
HCl
H
N
1. Cherkasov, R.A., Garifzyanov, A.R., Koshkin, S.A., and
Davletshina, N.V., Russ. J. Gen. Chem., 2012, vol. 82,
p. 1453.
–NaCl
(S)-III
624