New simple synthesis of N-substituted 1,3-oxazinan-2-ones

Article abstract of DOI:10.1055/s-0029-1218642

An efficient and simple synthesis of N-substituted 1,3-oxazinan-2-ones was developed that involves a three-component, one-pot reaction of readily available tetraethylammonium bicarbonate, 1,3-dibromopropane, and a primary amine in methanol at room temperature. l-Alanine can be used as the amino component to give the chiral product (2S)-2-(2-oxo-1,3-oxazinan-3-yl)propanoic acid. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0029-1218642

PAPER
943
New Simple Synthesis of N-Substituted 1,3-Oxazinan-2-ones
O
xazinanonesrećko Trifunović,a Dejana Dimitrijević,a Gordana Vasić,a Niko Radulović,b Mirjana Vukićević,c
Frank W. Heinemann,d Rastko D. Vukićević*a
a
Department of Chemistry, Faculty of Science, University of Kragujevac, R. Domanovića 12, 34000 Kragujevac, Serbia
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia
Department of Pharmacy, Medical Faculty, University of Kragujevac, S. Markovića 69, 34000 Kragujevac, Serbia
Department of Chemistry and Pharmacy, Friedrich-Alexander-University Erlangen-Nuremberg, Egerlandstr. 1, 91058 Erlangen,
b
c
d
Germany
Fax +381(34)335040; E-mail: vuk@kg.ac.rs
Received 19 October 2009; revised 20 November 2009
can also be achieved by using 3-chloropropanol as the
starting material, via the chloroformyl ester and the car-
bamate,15 or by reaction with cyanate ion in anhydrous
N,N-dimethylformamide.16 3-Bromopropan-1-amine, on
Abstract: An efficient and simple synthesis of N-substituted 1,3-
oxazinan-2-ones was developed that involves a three-component,
one-pot reaction of readily available tetraethylammonium bicarbon-
ate, 1,3-dibromopropane, and a primary amine in methanol at room
temperature. L-Alanine can be used as the amino component to give the other hand, can be converted into unsubstituted 1,3-
the chiral product (2S)-2-(2-oxo-1,3-oxazinan-3-yl)propanoic acid.
oxazinan-2-one by treatment with tetraethylammonium
bicarbonate,17 or by the electrochemical reduction of oxy-
Key words: cyclizations, urethanes, oxazinanones, amines
gen in the presence of the substrate and carbon dioxide.18
Six-membered cyclic urethanes and their derivatives can
1,3-Oxazinan-2-ones, which are six-membered cyclic
urethanes, are an important class of compounds that can
serve as small building blocks for the synthesis of phar-
maceutical compounds1 or 1,3-amino alcohols.2 Although
there are only a few reports in the literature on the synthe-
sis of nonurethane 1,3-oxazinanes,3 several types of start-
ing substrate have been used in syntheses of 1,3-oxazinan-
2-one or its derivatives. All the reactions used in these
syntheses can be divided into two groups: intermolecular
cyclizations or intramolecular cyclizations.
also be prepared by intramolecular cyclization reactions,
such as the reaction of 1-chloro-3-isocyanatopropane with
bis(tributyltin) oxide,19 Hofmann rearrangements of 4-hy-
droxy amides,20 Curtius rearrangements of 4-hydroxy hy-
drazides,21 thermolyses of 4-hydroxy N-ammonio
amidates22 or alkyl azidoformates,23 halocyclizations of
allyl,24 homoallyl,2,25 or allenyl26 carbamates, halocycliza-
tion of allyl amines in the presence of carbon dioxide,27 or
Sharpless asymmetric dihydroxylation of homoallylic
carbamates.28
The starting materials that are used for the first group of
reactions are mainly 1,3-bifunctional compounds in
which at least one functional group contains an oxygen or
nitrogen atom, and in most cases the substrates are com-
pounds containing both oxygen and nitrogen separated by
the same distance as that in the target molecule. Thus, 1,3-
oxazinan-2-one or its derivatives have been prepared by
the reaction of 1,3-amino alcohols with carbonic acid de-
rivatives such as ethylene carbonate,4 urea,5 1,1¢-carbon-
yldiimidazole,6 or triphosgene.3b,c The insertion of a
carbonyl group between the oxygen and nitrogen atoms in
these substrates to give the required six-membered cyclic
urethanes has also been achieved by reaction with carbon
monoxide catalyzed by palladium(II) complexes7 or
selenium8 or with carbon dioxide catalyzed by phospho-
rus(III) reagents, in carbon tetrachloride or perchloro-
ethane.9 Trichloroacetates,10 trifluoroacetamides,11 or N-
benzyloxycarbonyl derivatives12 of 1,3-amino alcohols,
as well as their N-tert-butoxycarbonyl tosylates13 and N-
aroyl nitrates,14 can likewise be converted into 1,3-oxazi-
nan-2-ones. Synthesis of six-membered cyclic urethanes
Here we report a new, simple synthesis of N-substituted
six-membered cyclic urethanes from 1,3-dibromopro-
pane, tetraethylammonium bicarbonate, and a primary
amine. Thus, a methanolic solution of 1,3-dibromopro-
pane (1), benzylamine (2a, Scheme 1), and commercially
available tetraethylammonium bicarbonate was refluxed
for one hour to give a mixture from which N-benzyl-1,3-
oxazinan-2-one (3a) was isolated in 15% yield by evapo-
ration of the solvent, dissolution of the residue in 2 M hy-
drochloric acid, and extraction with diethyl ether.
O
O
R
Br
MeOH
+
Et4NHCO3
+
RNH2
N
Br
1
2a–i
3a–i
a R = benzyl
b R = 2-thenyl
c R = 2-phenylethyl
d R = 2-(4-methoxyphenyl)ethyl
e R = phenyl
f R = 4-tolyl
g R = cyclohexyl
h R = octyl
i R = dodecyl
j R = tert-butyl
Scheme 1 Synthesis of N-substituted 1,3-oxazinan-2-ones
The composition of the crude reaction mixture was ana-
lyzed in detail by gas chromatography–mass spectrometry
(GC/MS) and quantified by estimations of the areas under
SYNTHESIS 2010, No. 6, pp 0943–0946
Advanced online publication: 12.01.2010
DOI: 10.1055/s-0029-1218642; Art ID: T20509SS
x
x
.
x
x
.2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

944
S. Trifunović et al.
PAPER
the peaks of the total ion chromatograms, which are ex-
pressed as the corresponding relative percentage. This
analysis showed that the mixture consisted mainly of the
unchanged starting reagents (dibromide 1 and primary
amine 2a), together with the oxazinanone 3a (about 20%).
The mixture also contained small amounts of several other
components. Although the mass spectral fragmentation
patterns in GC/MS analysis are insufficient to give an un-
ambiguous identification of a compound, we believe that
among these components were 3-bromopropanol (traces),
3-methoxy-1-bromopropane (traces), 1-benzylazetidine
(up to 1.5%), N-benzyl-3-bromopropan-1-amine (traces),
and 3-bromopropyl benzylcarbamate (up to 1.5%).
Table 1 Synthesis of N-Substituted 1,3-Oxazinan-2-ones 3a–i
Entry
Amine
2a
Oxazinanone
Yield (%)
1
2
3a
3b
3c
3d
3e
3f
60
61
57
54
–
2b
2c
3
4
2d
2e
5
6
2f
7
7
2g
3g
3h
3i
80
62
52
–
Prolonged heating of the mixture resulted in increased
amounts of oxazinan-2-one and a compound that we iden-
tified as 1-benzylazetidine (up to about 60 and 3.5%, re-
spectively, after refluxing for six hours), whereas the
compounds that we tentatively identified as N-benzyl-3-
bromopropan-1-amine and 3-bromopropyl benzylcar-
bamate had almost completely disappeared.
8
2h
2i
9
10
2j
–
vent is capable of dissolving all three reaction components
(L-alanine, 1,3-dibromopropane, and a bicarbonate), we
decided to use a combination of two miscible solvents,
water and ethanol, because L-alanine is soluble in aqueous
potassium bicarbonate solution, whereas 1,3-dibromopro-
pane soluble in ethanol. When a solution of 1,3-dibro-
mopropane in ethanol was added dropwise to a boiling
aqueous solution of L-alanine and potassium bicarbonate,
the target urethane (S)-2-(2-oxo-1,3-oxazinan-3-yl)pro-
panoic acid (3k) was obtained in 32% isolated yield
(Scheme 2).
The best yield of compound 3a (60%) was achieved when
the mixture was kept at room temperature overnight. 3-
Benzyl-1,3-oxazinan-2-one (3a) was easily isolated from
the acidic mixture and characterized by spectral methods,
since the unconsumed 1,3-dibromopropane was removed
by evaporation under in a vacuum, and the starting amine
2 was washed out as its water-soluble salt, which was in-
soluble in ether. The absence of the component that we
identified as 1-benzylazetidine in the ethereal extract con-
firmed its basic character.
Several primary amines were then submitted to the same
reaction conditions. The results for these reactions are list-
ed in Table 1. The benzylic-type amine 2b and amines 2c
and 2d behaved similarly to benzylamine, giving the cor-
responding N-substituted 1,3-oxazinan-2-ones (3b–d, re-
spectively) in moderate isolated yields. Two aromatic
amines, aniline (2e) and p-toluidine (2f), were found to be
unsuitable as substrates for this reaction. Although both of
these amines gave the corresponding oxazinanones ac-
cording to GC/MS analysis, we were able to isolate only
the toluidine derivative 3f in a low yield. A high yield of
the cyclic urethane was achieved when cyclohexanamine
was used as the substrate, whereas the aliphatic amines 2h
and 2i gave the corresponding cyclic urethanes in similar
yields to amines 2a–d. Surprisingly, 2-methylpropan-2-
amine (2j) did not react at all.
Br
O
O
NH2
COOH
KHCO3
+
EtOH–H2O
Br
N
COOH
1
2k
3k
Scheme 2 Synthesis of (2S)-2-(2-oxo-1,3-oxazinan-3-yl)propanoic
acid (3k)
The structure of (2S)-2-(2-oxo-1,3-oxazinan-3-yl)pro-
panoic acid (3k) was confirmed by X-ray analysis (see
Figure 1).29
We believe that the probable intermediates in this reaction
are 3-bromopropyl benzylcarbamate and N-benzyl-3-bro-
mopropan-1-amine, because we observed these two com-
ponents in the reaction mixtures at an early stage, but they
disappeared as the reaction progressed.
Because of the possible applications of 1,3-oxazinan-2-
ones in asymmetric syntheses, we considered the possibil-
ity of using a chiral amino acid as the amine component of
our reaction. L-Alanine (2k), the most readily available
chiral amino acid, was chosen, but it was necessary to
adapt our procedure for this substrate. As no suitable sol-
Figure 1 Thermal ellipsoid plot of 3k showing ellipsoids at the 50%
probability level
Synthesis 2010, No. 6, 943–946 © Thieme Stuttgart · New York

PAPER
Oxazinanones
945
IR (neat): 3024, 2930, 1669, 1519, 1447, 1280, 1115, 1011, 755,
725, 700 cm–1.
simple, can be conducted in any laboratory, and requires 1H NMR (CDCl3): d = 1.90 (m, 2 H), 2.94 (t, J = 6.2 Hz, 2 H), 3.07
In summary, we have developed a new method for the
synthesis of N-substituted 1,3-oxazinan-2-ones that is
(t, J = 7.2 Hz, 2 H), 3.51 (t, J = 7.2 Hz, 2 H), 4.14 (t, J = 5.3 Hz, 2
H), 7.19–7.33 (m, 5 H).
13C NMR (CDCl3): d = 21.7, 33.1, 45.6, 50.9, 66.0, 126.0, 128.1,
128.4, 138.4, 153.0.
MS (EI, 70 eV): m/z (%) = 114 (100), 104 (66), 205 (62) [M]+, 42
(61), 91 (42), 70 (32), 41 (26), 65 (14), 77 (13), 105 (13).
only cheap and readily available starting materials. The
most important advantage of the method is ease of separa-
tion and purification of the oxazinanone products from the
reaction mixtures, which require only extraction and
evaporation procedures.
Anal. Calcd for C12H15NO2 (205.25): C, 70.22; H, 7.37; N, 6.82.
Found: C, 70.16; H, 7.44; N, 6.81.
All starting materials were obtained from commercial suppliers (Al-
drich, Fluka, Merck) and were used without further purification.
The solvents were purified by distillation. Melting points (uncor-
rected) were determined on a Mel-Temp capillary melting points
apparatus (Model 1001). The 1H and 13C NMR spectra of samples
dissolved in CDCl3 or DMSO-d6 were recorded on a Varian Gemini
(200 MHz) spectrometer. Chemical shifts are expressed in d (ppm),
relative to residual solvent protons as internal standards (CDCl3:
d = 7.26 ppm for 1H; d = 77 ppm for 13C; DMSO-d6: d = 2.50 ppm
3-[2-(4-Methoxyphenyl)ethyl]-1,3-oxazinan-2-one (3d)
Colorless solid; yield: 54%; mp 87–88 °C.
IR (neat): 3032, 2925, 1685, 1672, 1612, 1441, 1237, 1116, 1032,
756 cm–1.
1H NMR (CDCl3): d = 1.83 (m, 2 H), 2.78 (t, J = 7.3 Hz, 2 H), 3.01
(t, J = 6.2 Hz, 2 H), 3.41 (t, J = 7.3 Hz, 2 H), 3.71 (s, 3 H), 4.10 (t,
J = 7.3 Hz, 2 H), 6.74–6.78 (m, 2 H), 7.05–7.10 (m, 2 H).
1
for H, d = 39.43 ppm for 13C). IR spectra were recorded on a
Perkin-Elmer FTIR 31725-X spectrophotometer. Microanalyses of
carbon, hydrogen, nitrogen, and sulfur were carried out with a Carlo
Erba 1106 microanalyzer; the results agreed well with the calculat-
ed values. The GC/MS analyses were carried out by using a
Hewlett-Packard 6890N gas chromatograph equipped with a fused
silica capillary column HP-5MS [5% phenyl(methyl)siloxane, 30 m
× 0.25 mm, film thickness 0.25 mm, Agilent Technologies, USA]
coupled to a Hewlett-Packard 5975B mass-selective detector. The
injector and interface were operated at 250 °C and 300 °C, respec-
tively. The oven temperature was increased from 70 to 290 °C at
5 °C min–1 and then held for 10 min. The carrier gas was He at a
flow rate of 1.0 mL min–1. The samples were injected in a pulsed
split mode at 1.5 mL min–1 for the first 0.5 min and then 1.0 mL
min–1 throughout the remainder of the analysis at a split ratio of
40:1. MS conditions were as follows: ionization voltage 70 eV, ac-
quisition mass range 35–500, scan time 0.32 s. Optical rotations
were measured on a Perkin-Elmer SP Polarimeter.
13C NMR (CDCl3): d = 22.1, 32.6, 46.0, 51.5, 55.1, 66.2, 113.8,
129.7, 130.8, 153.3, 158.1.
MS (EI, 70 eV): m/z (%) = 134 (100), 121 (24), 42 (12), 135 (11),
91 (6), 41 (6), 119 (6), 77 (6), 78 (6), 235 (4) [M]+.
Anal. Calcd for C13H17NO3 (235.28): C, 66.36; H, 7.28; N, 5.95.
Found: C, 66.21; H, 7.22; N, 5.95.
3-Phenyl-1,3-oxazinan-2-one (3e)
Not isolated.
MS (EI, 70 eV): m/z (%) = 104 (100), 77 (82), 177 (74) [M]+, 105
(43), 91 (38), 132 (33), 51 (20), 119 (11), 78 (8), 178 (8).
3-Cyclohexyl-1,3-oxazinan-2-one (3g)
Colorless solid; yield: 80%; mp 60–61 °C.
IR (neat): 2927, 2852, 1666, 1484, 1432, 1286, 1108, 756 cm–1.
1H NMR (CDCl3): d = 1.03–1.17 (m, 1 H), 1.34–1.48 (m, 4 H),
1.72–1.82 (m, 5 H), 2.0 (m, 2 H), 3.23 (t, J = 6.1 Hz, 2 H), 4.07–4.17
(m, 1 H), 4.21 (t, J = 5.3 Hz, 2 H).
13C NMR (CDCl3): d = 22.2, 25.4, 25.5, 29.4, 39.3, 55.5, 65.8,
153.2.
N-Substituted 1,3-Oxazinan-2-ones 4a–j; General Procedure
Et4NHCO3 (3.82 g, 20 mmol), Br(CH2)3Br (2.02 g, 10 mmol), and
an amine 2a–j (10 mmol) were dissolved in MeOH (20 mL) and the
mixture was stirred overnight at r.t. MeOH and residual Br(CH2)3Br
(if present) were evaporated in vacuo, and the resulting oily mass
was diluted with 1 M H2SO4 (20 mL). The mixture was extracted
with several 20-mL portions of Et2O, and the combined organic lay-
ers were dried (Na2SO4) and concentrated. The resulting oxazi-
nanones were sufficiently pure for spectroscopic analysis.
Compounds 3a and 3f are known, and their spectral data have been
reported elsewhere.19,30
MS (EI, 70 eV): m/z (%) = 102 (100), 140 (68), 56 (43), 41 (37), 183
(34) [M]+, 55 (31), 74 (24), 54 (22), 68 (16), 39 (13).
Anal. Calcd for C10H17NO2 (183.25): C, 65.54; H, 9.35; N, 7.64.
Found: C, 65.63; H, 9.40; N, 7.69.
3-Octyl-1,3-oxazinan-2-one (3h)
Colorless semi-solid; yield: 62%.
3-(2-Thienylmethyl)-1,3-oxazinan-2-one (3b)
Colorless solid; yield: 61%; mp 128–130 °C.
IR (neat): 3054, 2969, 2925, 1681, 1537, 1264, 1131, 691, 630 cm–1.
1H NMR (CDCl3): d = 2.00 (m, 2 H), 3.31 (t, J = 6.2 Hz, 2 H), 4.23
(t, J = 5.4 Hz, 2 H), 4.68 (s, 2 H), 6.93–7.02 (m, 2 H), 7.23–7.26 (m,
1 H).
13C NMR (CDCl3): d = 22.1, 44.1, 47.2, 66.4, 125.6, 126.6, 126.8,
138.9, 153.4.
MS (EI, 70 eV): m/z (%) = 97 (100), 197 (60) [M]+, 152 (52), 124
IR (neat): 2922, 2854, 1652, 1534, 1466, 1215, 1025, 724, 576 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 6.5 Hz, 3 H), 1.27 (m, 12 H),
1.40–1.66 (m, 2 H), 2.04 (m, 2 H), 3.31 (t, J = 6.4 Hz, 2 H), 4.25 (t,
J = 5.4 Hz, 2 H).
13C NMR (CDCl3): d = 14.0, 22.2, 22.5, 26.6, 27.0, 29.1, 29.2, 31.7,
45.0, 49.6, 66.5, 153.9.
MS (EI, 70 eV): m/z (%) = 114 (100), 42 (47), 115 (45), 70 (37), 41
(34), 142 (22), 184 (18), 156 (14), 43 (13), 213 (13) [M]+.
(35), 110 (33), 45 (15), 41 (12), 53 (11), 125 (10), 39 (9).
Anal. Calcd for C12H23NO2 (213.32): C, 67.57; H, 10.87; N, 6.57.
Found: C, 67.50; H, 10.84; N, 6.69.
Anal. Calcd for C9H11NO2S (197.25): C, 54.80; H, 5.62; N, 7.10; S,
16.26. Found: C, 54.67; H, 5.68; N, 7.01; S, 16.22.
3-Dodecyl-1,3-oxazinan-2-one (3i)
Colorless semi-solid; yield: 52%.
3-(2-Phenylethyl)-1,3-oxazinan-2-one (3c)
Colorless solid; yield: 57%; mp 65–67 °C.
Synthesis 2010, No. 6, 943–946 © Thieme Stuttgart · New York

946
S. Trifunović et al.
PAPER
(6) (a) Caggiano, L.; Fox, D. J.; Warren, S. Chem. Commun.
IR (neat): 2919, 2851, 1681, 1533, 1497, 1247, 1220, 1146, 1039,
871, 721, 574 cm–1.
2002, 2528. (b) Ella-Menye, J.-R.; Sharma, V.; Wang, G.
J. Org. Chem. 2005, 70, 463.
1H NMR (CDCl3): d = 0.88 (t, J = 6.4 Hz, 3 H), 1.26 (m, 20 H),
1.40–1.68 (m, 2 H), 2.03 (m, 2 H), 3.31 (t, J = 6.3 Hz, 2 H), 4.24 (t,
J = 5.04 Hz, 2 H).
13C NMR (CDCl3): d = 14.0, 22.3, 22.6, 26.7, 27.0, 29.2, 29.3, 29.3,
29.5, 29.6, 29.6, 31.8, 45.1, 49.6, 66.4, 153.7.
(7) Giannoccaro, P.; Dibenedetto, A.; Gargano, M.; Quaranta,
E.; Aresta, M. Organometallics 2008, 27, 967.
(8) Sonoda, N.; Yamamoto, G.; Naysukawa, K.; Kondo, K.;
Murai, S. Tetrahedron Lett. 1975, 16, 1969.
(9) Kubata, Y.; Kodaka, M.; Tomohiro, T.; Okano, H. J. Chem.
Soc., Perkin Trans. 1 1993, 5.
(10) Lesher, G. Y.; Surrey, A. R. J. Am. Chem. Soc. 1955, 77,
636.
(11) Ella-Menye, J.-R.; Wang, G. Tetrahedron 2007, 63, 10034.
(12) Lohray, B. B.; Baskaran, S.; Reddy, B. Y.; Rao, K. S.
Tetrahedron Lett. 1998, 39, 6555.
(13) Curran, T. P.; Pollastri, M. P.; Abelleira, S. M.; Messier, R.;
McCollum, T. A.; Rowe, C. G. Tetrahedron Lett. 1994, 35,
5409.
(14) Korepin, A. G.; Galkin, P. V.; Glushakova, N. M.;
Perepelkina, E. K.; Loginova, M. V.; Lodygina, V. P.;
Ol’khov, Yu. A.; Eremenko, L. T. Russ. Chem. Bull. 2003,
52, 2221.
(15) Pierce, J.; Adams, R. J. Am. Chem. Soc. 1923, 45, 790.
(16) Phillips, B. L.; Argabright, P. A. Heterocycl. Chem. 1966, 3,
84.
(17) Inesi, A.; Mucciante, V.; Rossi, L. J. Org. Chem. 1998, 63,
1337.
(18) Casadei, M. A.; Moracci, F. M.; Zappia, G.; Inesi, A.; Rossi,
L. J. Org. Chem. 1997, 62, 6754.
(19) Shibata, I.; Nakamura, K.; Baba, A.; Matsuda, H. Bull.
Chem. Soc. Jpn. 1989, 62, 853.
(20) (a) Park, M.-S.; Lee, J.-W. Arch. Pharmacal Res. 1993, 16,
158. (b) Hilborn, J. W.; Lu, Z.-H.; Jurgens, A. R.; Fang, Q.
K.; Byers, P.; Wald, S. A.; Senanayake, C. H. Tetrahedron
Lett. 2001, 42, 8919. (c) Hernandez, E.; Velez, J. M.; Vlaar,
C. P. Tetrahedron Lett. 2007, 48, 8972.
(21) Sullivan, J. M.; Efner, H. F. J. Org. Chem. 1968, 33, 2134.
(22) Masuyama, A.; Tsuchiya, K.; Okahara, M. Bull. Chem. Soc.
Jpn. 1985, 58, 2855.
MS (EI, 70 eV): m/z (%) = 114 (100), 115 (51), 70 (31), 42 (30), 41
(25), 142 (24), 240 (19), 156 (19), 269 (15) [M]+, 43 (15).
Anal. Calcd for C16H31NO2 (269.42): C, 71.33; H, 11.60; N, 5.20.
Found: C, 71.35; H, 11.52; N, 5.11.
(2S)-2-(2-Oxo-1,3-oxazinan-3-yl)propanoic Acid (3k)
L-Alanine (8.9 g, 0.1 mol) was added to a soln of KHCO3 (30 g, 0.3
mol) in H2O (60 mL), and the mixture was heated to reflux. A soln
of Br(CH2)3Br (2.02 g, 10 mmol) in EtOH (20 mL) was slowly add-
ed dropwise to the clear boiling mixture over 1 h. The mixture was
refluxed for a further 5 h, then concentrated to 60 mL by evapora-
tion in vacuo, acidified to pH 3.5, and kept at r.t. overnight. The pre-
cipitate was filtered off, washed with EtOH and Et2O, and dried
(CaCl2) to give 3k; yield: 5.6 g (32 mmol; 32%); mp 210 °C (H2O);
[a]D20 –4.40 (c 0.5%, H2O). For X-ray crystal structure analysis, the
product was recrystallized (H2O).
IR (KBr): 3431, 3266, 2911, 2582, 1728, 1654, 1639, 1502, 1305,
1248, 1086, 960, 767 cm–1.
1H NMR (DMSO-d6): 1.32 (d, J = 7.4 Hz, 3 H), 1.86–1.99 (m, 2 H),
3.13–3.40 (m, 2 H) 4. 16 (t, J = 5.5 Hz, 2 H), 4.51 (q, J = 7.4 Hz, 1
H).
13C NMR (DMSO-d6): 14.2, 22.0, 42.3, 54.8, 66.5, 153.2, 173.3.
MS (EI, 70 eV): m/z (%) = 128 (100), 84 (73), 56 (70), 41 (65), 42
(36), 114 (27), 70 (22), 44 (20), 129 (16), 45 (15), 173 (12) [M]+.
Anal. Calcd for C7H11NO4 (173.17): C, 48.55; H, 6.40; N, 8.09;
Found: C, 47.98; H, 6.40; N, 8.13.
(23) (a) Breslow, D. S.; Ward, G. A. J. Org. Chem. 1973, 38,
4205. (b) Alewood, P. F.; Benn, M.; Reinfried, R. Can. J.
Chem. 1974, 52, 4083. (c) Edwards, O. E.; Paryzek, Z. Can.
J. Chem. 1973, 51, 3866.
Acknowledgment
This work was supported by the Ministry of Science and Technolo-
gical Development of the Republic of Serbia (Grant 142042).
(24) Jordá-Gregori, J. M.; González-Rosende, M. E.; Sepúlveda-
Arques, J.; Galeazzi, R.; Orena, M. Tetrahedron: Asymmetry
1999, 10, 1135.
References
(25) (a) Fujita, M.; Kitagawa, O.; Suzuki, T.; Taguchi, T. J. Org.
Chem. 1997, 62, 7330. (b) Hayes, C. J.; Beavis, P. W.;
Humphries, L. A. Chem. Commun. 2006, 4501.
(26) Kang, S.-K.; Baik, T.-G.; Hur, Y. Tetrahedron 1999, 55,
6863.
(27) Garcia-Egido, E.; Fernández, I.; Muñoz, L. Synth. Commun.
2006, 36, 3029.
(28) (a) Walsh, P. J.; Bennani, Y. L.; Sharpless, K. B.
Tetrahedron Lett. 1993, 34, 5545. (b) Donohoe, T. J.;
Johnson, P. D.; Pye, R. J. Org. Biomol. Chem. 2003, 1, 2025.
(29) Crystallographic data for compound 3k have been deposited
with the Cambridge Crystallographic Data Centre as
supplementary publication CCDC 736836; copies can be
obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or
email: deposit@ccdc.cam.ac. uk].
(1) Wang, G.; Ella-Menye, J.-R.; Sharma, V. Bioorg. Med.
Chem. Lett. 2006, 16, 2177.
(2) Bogini, A.; Cardillo, G.; Orena, M.; Poorzi, G.; Sandrini, S.
Chem. Lett. 1988, 87.
(3) (a) D’hooghe, M.; Dekeukeleire, S.; Mollet, K.; Lategan, C.;
Smith, P. J.; Chibale, K.; De Kimpe, N. J. Med. Chem. 2009,
52, 4058; and references cited therein. (b) Zanatta, N.;
Squizani, A. M. C.; Fantinel, F.; Nachtigall, F. M.;
Borchhardt, D. M.; Bonacorso, H. G.; Martins, M. A. P.
J. Braz. Chem. Soc. 2005, 16, 1255. (c) Sainsbury, M. In
Comprehensive Heterocyclic Chemistry, Vol. 3; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon: Oxford, 1984, 995.
(4) Dyer, E.; Scott, H. J. Am. Chem. Soc. 1957, 79, 672.
(5) (a) Kim, Y. J.; Varma, R. Tetrahedron Lett. 2004, 45, 7205.
(b) Bhanage, B. M.; Fujita, S.-i.; Ikushima, Y.; Arai, M.
Green Chem. 2004, 6, 78.
(30) Baba, A.; Kishiki, H.; Shibata, I.; Matsuda, H.
Organometallics 1985, 4, 1329.
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