Synthesis of 5-[bromo(aryl)methyl]-2,2-dimethyl-1,3-oxazolidin-4-ones

Article abstract of DOI:10.1007/s11172-016-1445-5

A Darzens condensation of α-chloroacetamide with aromatic aldehydes furnished a series of 3-aryl-2,3-epoxypropionamides, which were further converted to 5-[bromo(aryl)methyl]-2,2-dimethyl-1,3-oxazolidin-2-ones.

Full text of DOI:10.1007/s11172-016-1445-5

Russian Chemical Bulletin, International Edition, Vol. 65, No. 5, pp. 1260—1267, May, 2016
1260
Synthesis of 5ꢀ[bromo(aryl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀones*
V. A. Mamedov,a,b V. L. Mamedova,a,b G. Z. Khikmatova,a,b D. B. Krivolapov,a and I. A. Litvinova
aA. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences,
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
Fax: +7 (843) 275 532. Eꢀmail: mamedov@iopc.ru
bKazan National Research Technological University,
68 ul. K. Marksa, 420015 Kazan, Russian Federation
A Darzens condensation of αꢀchloroacetamide with aromatic aldehydes furnished a series
of 3ꢀarylꢀ2,3ꢀepoxypropionamides, which were further converted to 5ꢀ[bromo(aryl)methyl]ꢀ
2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ2ꢀones.
Key words: 3ꢀarylꢀ2,3ꢀepoxypropionamides, 3ꢀbromoꢀ2ꢀhydroxyꢀ3ꢀarylpropionamides,
5ꢀ[bromo(aryl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀones, 5ꢀ(arylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀ
oxazolidinꢀ4ꢀones, diastereomers, Xꢀray diffraction analysis.
An oxazolidine ring is a part of such pharmaceutiꢀ
cal drugs as trimethin1 (anticonvulsant), furazolidone
and furazoline2 (antimicrobial agents), linezolid3 (synthetꢀ
ic antibiotic). An oxazolidine ring in the composition
of fused polycyclic systems is a part of ergotamine and
bromocriptine, which are widely used in obstetric and
gynecological practice,2 as well as in quinocarcin suggestꢀ
ed4 for treatment of leukemia. Nꢀ(2ꢀChloroethyl)oxꢀ
azolidinꢀ2ꢀone is a metabolite of antitumor agent cycloꢀ
phosphane (Scheme 1), whereas benzoxazolidinꢀ2ꢀone
* Dedicated to Academician of the Russian Academy of Sciences O. G. Sinyashin on the occasion of his 60th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1260—1267, May, 2016.
1066ꢀ5285/16/6505ꢀ1260 © 2016 Springer Science+Business Media, Inc.

1,3ꢀOxazolidinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1261
Scheme 1
Scheme 2
Scheme 3
was used in the synthesis of antidepressant azaphene
(Scheme 2).1
1,3ꢀOxazolidinꢀ4ꢀones are of interest not only from
the point of view of their biological activity, but also as the
starting compounds for the preparation of αꢀhydroxy
acids.5—8 The last mentioned compounds are widely used
in synthetic organic chemistry,9 and there is no doubt in
the importance of the development of simple methods for
the preparation of their various representatives. Due to the
development of asymmetric synthesis, the interest to oxꢀ
azolidinꢀ4ꢀone derivatives with chiral C(5) atom has
grown. It was shown7,8 that hydrolysis of enantiopure oxꢀ
azolidinone derivatives occurred with retention of configꢀ
uration at atom C(5) and the formation of enantiopure
forms of αꢀhydroxy acids (Scheme 3).
1,3ꢀOxazolidinꢀ4ꢀones are commonly obtained upon
treatment of α-hydroxy acid anilides with carbonyl comꢀ
pounds.10—15 This method, which uses available and inexꢀ
pensive starting material, gives oxazolidinones with a limꢀ
ited set of substituents at position 5. However, these are
the substituents, which determine the variety of αꢀhydroxy
acids obtained from oxazolidines, therefore, the developꢀ
ment of simple approaches to the synthesis of new 5ꢀsubꢀ
stituted oxazolidine derivatives from available material is
an actual problem. In the present work, we describe the synꢀ
thesis (Scheme 4) of 5ꢀ[bromo(aryl)methyl]ꢀ2,2ꢀdimeꢀ
thyloxazolidinꢀ4ꢀones 3 from 3ꢀarylꢀ2,3ꢀepoxypropionꢀ
amides 1. The last mentioned compounds, in turn, are easily
obtained by the reaction of chloroacetamide with aromatic
aldehydes under mild conditions of Darzens reaction.
Results and Discussion
3ꢀArylꢀ2,3ꢀepoxypropionamides 1a—e (Scheme 4,
Table 1) were synthesized under conditions of Darzens
condensation (NaOEt, NaOH) at room temperature from
the corresponding aromatic aldehydes and α-chloroacetꢀ
amide. Under these conditions, epoxypropionamides are
predominantly obtained as Eꢀisomers.16

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Mamedov et al.
Table 1. Synthesis of 3ꢀarylꢀ2,3ꢀepoxypropionamides 1a—e
are analogs of natural alkaloid compounds. The same reꢀ
sult was obtained when 3ꢀarylꢀ2,3ꢀepoxypropionanilides
were treated with sulfuric acid upon heating in dimethyl
sulfate or refluxed in benzene with azeptropic removal
of water.16 In the present work, replacing an anilide
fragment in the starting compounds with the amide group,
we exclude a possibility of the formation of the quinoline
systems.
Amides of (E)ꢀ3ꢀarylꢀ2,3ꢀepoxypropionic acid Eꢀ1,
like its anilides,19 were treated with HBr in acetone at
room temperature for 1 h (see Scheme 4). The reaction of
Eꢀ1a with HBr in acetone for 24 h led to a mixture of synꢀ
(δ 4.82, 5.41 (both d, J = 2.6 Hz)) and antiꢀdiastereomers
(δ 4.63, 5.44 (both d, J = 1.7 Hz)) of oxazolidinone 3a in
about 1 : 1 ratio. The diastereomer antiꢀ3a crystallized
from the reaction mixture within several minutes after
addition of water, whereas diastereomer synꢀ3a, only after
24 h. Amides Eꢀ1b and Eꢀ1c under similar conditions gave
mixtures of compounds containing both the hydrobromiꢀ
nated products and oxazolidinones. The reactions of
Eꢀ1d,e with HBr and acetone for 24 h at room temperaꢀ
ture proceeded diastereoselectively with the formation of
only synꢀdiastereomers 3d,e. The structure of synꢀ3e was
established by Xꢀray diffraction analysis (Fig. 1).
Comꢀ
pound
Yield
(%)
Ratioa
Z : E
Yield of isomersb (%)
Z
E
1a17,18
1b
1c
1d
1e
192
198
187
199
100
1 : 2
1 : 5
1 : 5
0 : 1
0 : 1
20
158
179
169
199
100
c
—
—
d
—
—
a 1H NMR spectroscopy data.
b Yields of isolated isomers.
c After isolation of Eꢀisomer, a mixture of Zꢀ1b : Eꢀ1b = 1 : 1 was
obtained in 19% yield.
d After isolation of Eꢀisomer, a mixture of Zꢀ1c : Eꢀ1c = 1 : 1 was
obtained in 18% yield.
Scheme 4
The conversion of arylepoxypropionamides 1 to oxꢀ
azolidinones 3 proceeds through hydrobrominated derivaꢀ
1—3: R = H (a), 4ꢀBr (b), 3ꢀMeO (c), 4ꢀF3C (d), 2ꢀO2N (e)
In the preceding works,16,19 we studied the behavior of
3ꢀarylꢀ2,3ꢀepoxypropionanilides under acidic conditions.
These compounds treated with HBr in acetone at room
temperature were quantitatively converted to anilides
(depending on the substituent in the aryl fragment) of
3ꢀbromoꢀ2ꢀhydroxyꢀ3ꢀphenylpropionic, 2ꢀbromoꢀ3ꢀhydrꢀ
oxyꢀ3ꢀphenylpropionic, or 3ꢀarylpyruvic acids.17 3ꢀBroꢀ
moꢀ2ꢀhydroxyꢀ3ꢀphenylpropionanilide heated to 100 °C
in dimethyl sulfate in the presence of sulfuric acid underꢀ
went intramolecular Friedel—Crafts reaction with the miꢀ
gration of the aryl group and aromatization of the bicyclic
system with the formation of 3ꢀarylquinolinꢀ2ꢀones, which
Fig. 1. Molecular geometry of synꢀ5ꢀ[bromo(2ꢀnitrophenyl)ꢀ
methyl]ꢀ2,2ꢀdimethyloxazolidinꢀ4ꢀone (synꢀ3e) in crystal acꢀ
cording to the Xꢀray diffraction data.

1,3ꢀOxazolidinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1263
Table 2. Synthesis of 3ꢀarylꢀ3ꢀbromoꢀ2ꢀhydroxypropionamides
2a—e
Table 3. Yields of 5ꢀ(αꢀbromobenzyl)ꢀ2,2ꢀdimethylꢀ
1,3ꢀoxazolidinꢀ4ꢀones 3a—e
Comꢀ
pound
Yield
(%)
Ratioa
syn : anti
Yield of isomersb (%)
Amide
Oxazolidinone
Yield (%)
syn
anti
synꢀ2а
antiꢀ2а
synꢀ2b
antiꢀ2b
synꢀ2c
antiꢀ2c
synꢀ2d
synꢀ2e
synꢀ3а
antiꢀ3а
synꢀ3b
antiꢀ3b
synꢀ3c
antiꢀ3c
synꢀ3d
synꢀ3e
98
90
96
92
88
92
89
92
2a
2b
2c
2d
2e
198
183
185
100
192
1 : 1
1 : 1
4 : 1
1 : 0
1 : 0
135
135
165
100
192
42
32
16
10
10
a 1H NMR spectroscopy data.
b Yields of isolated diastereomers.
from the only isolated from the reaction with HBr in dioxꢀ
ane diastereomer 2e are identical. This confirms the corꢀ
rectness of the assignment to diastereomer 2e of synꢀconꢀ
figuration (see Table 2).
Further, we made an attempt to transform the bromoꢀ
arylmethyl substituent at position 5 of oxazolidine cycle.
Stirring the solution of antiꢀ3a in MeOH with K2CO3 for
3 h at room temperature led to the formation of (Z)ꢀ5ꢀ
(benzylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀone (Zꢀ4a)
(Scheme 6, Table 4), the structure of which was estabꢀ
lished by Xꢀray diffraction study (Fig. 2).
tives 2 of starting epoxides (see Scheme 4). Compounds
2a—e (Table 2) were obtained by the reaction of the correꢀ
sponding epoxides with HBr in dioxane. These compounds
have two chiral centers and can exist in two diastereomeric
forms, easily distinguished by the signals for protons H(2) and
H(3) in the NMR spectra. The assignment of the signals to
synꢀ or antiꢀdiastereomers was made as described earlier.19
Each of the diastereomers 2a—c was isolated in the indiꢀ
vidual state, whereas compounds 2d and 2e were obtained
in the reactions only as synꢀdiastereomers (see Table 2).
The conditions for the cyclization of 3ꢀbromoꢀ2ꢀhydrꢀ
oxypropionamides 2 to oxazolidinones 3 were optimized
using synꢀ2a as a model. The reaction was carried out for
24 h in acetone either without acid or with the addition of
HBr, H2SO4, or AcOH. In the absence of acid, the reacꢀ
tion diastereoselectively proceeded on 77% (1H NMR
spectral data), when an acid was added, the reactions proꢀ
ceeded quantitatively and also diastereoselectively. The
cyclization of compounds 2b—e was carried out in aceꢀ
tone with the addition of H2SO4. The reactions were diaꢀ
stereoselective: the oxazolidinones obtained from synꢀ2
were assigned to synꢀ3 (Scheme 5), whereas antiꢀ2 gave
rise to antiꢀ3 (Table 3).
Scheme 6*
* Substituents R and configurations of starting compounds 3a—e
and products 4 are given in Table 4.
Similar conversions were carried out for synꢀ3a—e and
antiꢀ3a,c (see Table 4). The products were assigned to
Scheme 5
Table 4. Synthesis of 5ꢀ(arylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ
4ꢀones 4a—e and chemical shifts (δΗ) for the proton of the
RCH=C group in the 1H NMR spectra (DMSOꢀd6)
Starting
compound
Product
R
Yield
(%)
δ
H
(s)
synꢀ3а
antiꢀ3а
synꢀ3b
synꢀ3с
antiꢀ3с
synꢀ3d
synꢀ3е
Eꢀ4a + Zꢀ4a*
Zꢀ4а
Ph
Ph
173
189
183
179
192
100
100
6.20, 6.04
6.04
2, 3: R = Ph (a), 4ꢀBrC6H4 (b), 3ꢀMeOC6H4 (c), 4ꢀF3CC6H4 (d),
2ꢀO2NC6H4 (e)
Eꢀ4b
Eꢀ4с
Zꢀ4с
Eꢀ4d
4ꢀBrC6H4
3ꢀMeOC6H4
3ꢀMeOC6H4
4ꢀF3CC6H4
2ꢀO2NC6H4
6.18
6.18
6.00
6.28
Conditions: H2SO4, acetone, ~20 °C, 24 h.
Figure 1 shows the geometry of compound synꢀ3e obꢀ
tained directly from Eꢀ1e without isolation of the interꢀ
Eꢀ4е
6.29
1
mediate product 2e (see Scheme 4). H NMR and other
characteristics of this product and the product obtained
* The ratio of isomers Eꢀ4a : Zꢀ4a = 4 : 1 (1H NMR spectral data).

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Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
Mamedov et al.
tions were carried out using the WinGX22 and AРEХ223 programs.
Crystals of synꢀ3e, C12H13BrN2O4, are monoclinic. At 20 °C
a = 11.809(2), b = 13.814(3), c = 9.2415(18) Å, β = 110.38(3)°,
3
V = 1413.2(6) Å , Z = 4, dcalc = 1.547 g cm–3, space group P21/n,
μMo = 29.20 cm–1. There were measured intensities of 12037
reflections, 2263 of which were with I ≥ 2σ. The final divergence
factors were as follows: R = 0.0388, Rw = 0.0786. Crystals Zꢀ4a,
C12H13NO2, are monoclinic. At 20 °C a = 19.966(18),
3
b = 11.132(10), c = 15.339(14) Å, β = 97.743(15)°, V = 3378(5) Å ,
Z = 12 (there are three independent molecules in the asymmetric
part), dcalc = 1.199 g cm–3, space group P21/c, μMo = 0.82 cm–1
.
There were measured intensities of 6628 reflections, 2220 of
which were with I ≥ 2σ. The final divergence factors were as
follows: R = 0.1268, Rw = 0.2325. The Xꢀray diffraction data
were deposited with the Cambridge Crystallographic Data Center
(CCDC 1438779 (synꢀ3e) and CCDC 1438778 (Zꢀ4a).
a
a
3ꢀArylꢀ2,3ꢀepoxypropionamides (1a—e) were obtained simiꢀ
larly to the procedure described earlier19 for the anilides of this
acid. Equimolar amounts of αꢀchloroacetamide and the correꢀ
sponding benzaldehyde were mixed in EtOH at room temperaꢀ
ture, then an equimolar amount of NaOEt in EtOH was added,
and the reaction mixture was stirred for 5 h. A precipitate formed
was filtered, washed with water, and dried in air. An additional
amount of the precipitate was collected from the water—ethanol
filtrates after 15 h by filtration, washed with water, and dried.
Both precipitates corresponded to the product and were comꢀ
bined. Compounds 1a—c were obtained as mixtures of Zꢀ and Eꢀ
isomers. Isomers Eꢀ1a—c were isolated by washing these mixꢀ
tures with diethyl ether on a Schott funnel. The filtrates obtained
after washing the mixtures of isomers were concentrated, the
residues were washed with Et2O once more, and after evaporaꢀ
tion of the solvent, the individual Zꢀ1a and mixtures of Zꢀ and
Eꢀisomers of compounds 1b,c with the ratio of Z : E = 1 : 1 were
isolated. The yields of the products and the ratios of Zꢀ and
Eꢀisomers (in the initial mixtures) are given in Table 1.
Fig. 2. Geometries of three independent molecules of (Z)ꢀ5ꢀ
benzylideneꢀ2,2ꢀdimethyloxazolidinꢀ4ꢀone (Zꢀ4a) in crystal acꢀ
cording to the Xꢀray diffraction data.
Zꢀ or Eꢀisomers comparing their 1H NMR spectra with the
spectrum of Zꢀ4a, whose structure was known (see Fig. 2).
The spectra of the products contained mainly one signal
corresponding to the proton at the double bond that indiꢀ
cates the stereoselective character of the processes. In the
spectrum of the product obtained from synꢀ3a, the proton
at the double bond is represented by two signals with difꢀ
ferent intensities that is apparently explained by the forꢀ
mation of both isomers Zꢀ4a and Eꢀ4a (see Table 4).
In conclusion, in the presents the work we have develꢀ
oped an efficient method for diastereoselective synthesis
of 5ꢀ[bromo(aryl)methyl}ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ
4ꢀones, the representatives of pharmaceutically important
class of compounds.
(E)ꢀ2,3ꢀEpoxyꢀ3ꢀphenylpropionamide (Eꢀ1a). M.p. 142—144 °C
(cf. Ref. 17: 148 °C; cf. Ref. 18: 149.5—150 °C). Found (%):
C, 66.14; H, 5.52; N, 8.60. C9H9NO2. Calculated (%): C, 66.25;
H, 5.56; N, 8.58. IR, ν/cm–1: 1670 (C=O), 3405 (NH2). 1H NMR,
δ: 3.51, 4.03 (both d, 1 H each, H(2), H(3), J = 1.7 Hz); 7.28—7.42
(m, 5 H, Ph); 7.43, 7.61 (both br.s, 1 H each, NH2).
(Z)ꢀ2,3ꢀEpoxyꢀ3ꢀphenylpropionamide
(Zꢀ1a).
M.p.
139—140 °C. Found (%): C, 66.32; H, 5.58; N, 8.57. C9H9NO2.
Calculated (%): C, 66.25; H, 5.56; N, 8.58. IR, ν/cm–1: 1668
(C=O), 3408 (C(O)NH2). 1H NMR, δ: 3.74, 4.29 (both d,
1 H each, H(2), H(3), J = 4.5 Hz); 7.19 (br.s, 1 H, C(O)NH2);
7.20—7.45 (m, 6 H, Рh and NH).
(E)ꢀ2,3ꢀEpoxyꢀ3ꢀ(4ꢀbromophenyl)propionamide (Eꢀ1b). M.p.
178—179 °C. Found (%): C, 44.59; H, 3.32; Br, 33.08; N, 5.73.
C9H8BrNO2. Calculated (%): C, 44.66; H, 3.33; Br, 33.01;
N, 5.79. IR, ν/cm–1: 1661 (C=O), 3459 (C(O)NH2). 1H NMR,
δ: 3.50, 4.01 (both d, 1 H each, H(2); H(3), J = 1.7 Hz); 7.27,
7.54 (both d, 2 H each, Ar, J = 8.4 Hz); 7.42, 7.68 (both br.s,
1 H each, NH2). The signals for Zꢀ1b in the 1H NMR spectrum
(a mixture of Zꢀ1b : Eꢀ1b = 1 : 1), δ: 3.75, 4.28 (both d, 1 H each,
H(2), H(3), J = 5.0 Hz); 7,19, 7.43 (both br.s, 1 H each, NH2);
7.35, 7.51 (both d, 2 H each, Ar, J = 8.4 Hz).
Experimental
Melting points were determined using a Stuart SMPꢀ10 apꢀ
pliance. IR spectra were obtained on a Bruker Vectorꢀ22 spectroꢀ
meter in Nujol. 1H NMR spectra were recorded on a Bruker
Avanceꢀ600 spectrometer in DMSOꢀd6.
Xꢀray diffraction studies of crystals of synꢀ3e and Zꢀ4a grown
in ethanolic solutions were carried out on a Bruker Kappa Apex II
diffractometer (graphite monochromator, λMoKα = 0.71073 Å)
at 20 °C. Semiꢀempirical correction for absorption was performed
using the SADABS20 program. The structures were solved by
direct method using the SHELX21 program. Nonhydrogen atoms
were refined in isotropic and then in anisotropic approximation
using the SHELX21 program. Hydrogen atoms were placed in
calculated positions and refined using a riding model. The posiꢀ
tion of the hydrogen atom at the nitrogen atom in compound
synꢀ3e was found from the difference Fourier series and refined
in isotropic approximation in both structures. All the calculaꢀ
(E)ꢀ2,3ꢀEpoxyꢀ3ꢀ(3ꢀmethoxyphenyl)propionamide (Eꢀ1c).
M.p. 130—131 °C. C10H11NO3. Found (%): C, 62.08; H, 5.71;
N, 7.27. Calculated (%): C, 62.17; H, 5.74; N, 7.25. IR, ν/cm–1
:
1641 (C=O), 3392 (C(O)NH2). 1H NMR, δ: 3.50, 3.99 (both d,

1,3ꢀOxazolidinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1265
1 H each, H(2), H(3), J = 1.9 Hz); 3.68 (s, 3 H, OMe); 6.87 (s, 1 H,
H(2), Ar); 6.90 (br.d, 2 H, H(4) and H(6), Ar); 7.25 (dd, 1 H,
H(5), Ar, J = 8.1 Hz, J = 7.9 Hz). The signals for Zꢀ1c in the
1H NMR spectrum (a mixture of Zꢀ1c : Eꢀ1c = 1 : 1), δ: 3.73,
4.25 (both d, 1 H each, H(2), H(3), J = 4.9 Hz); 3.67 (s, 3 H,
OMe); 6.89 (s, 1 H, H(2), Ar), 6.93 (br.d, 2 H, H(4) and H(6),
Ar); 7.18, 7.50 (both br.s, 1 H each, NH2); 7.19 (dd, 1 H, H(5),
Ar, J = 7.9 Hz).
(E)ꢀ2,3ꢀEpoxyꢀ3ꢀ(4ꢀtrifluoromethylphenyl)propionamide
(Eꢀ1d). M.p. 171—172 °C. Found (%): C, 51.90; H, 3.42;
F, 24.87; N, 6.09. C10H8F3NO2. Calculated (%): C, 51.96; H, 3.49;
F, 24.65; N, 6.06. IR, ν/cm–1: 1672 (C=O), 3423 (C(O)NH2).
1H NMR, δ: 3.53, 4.17 (both d, 1 H each, H(2), H(3), J = 1.6 Hz);
7.47, 7.65 (both br.s, 1 H each, NH2); 7.57, 7.74 (both d, 2 H each,
Ar, J = 8.1 Hz).
(E)ꢀ2,3ꢀEpoxyꢀ3ꢀ(2ꢀnitrophenyl)propionamide (Eꢀ1e). M.p.
209—210 °C. Found (%): C, 52.02; H, 3.85; N, 13.43. C9H8N2O4.
Calculated (%): C, 51.93; H, 3.87; N, 13.46. IR, ν/cm–1: 1665
(C=O), 3185, 3368 (C(O)NH2). 1H NMR, δ: 3.39, 4.52 (both d,
1 H each, H(2), H(3), J = 1.9 Hz); 7.48, 7.69 (both br.s, 1 H each,
NH2); 7.53 (d, 1 H, H(6), Ar, J = 7.7 Hz); 7.65 (ddd, 1 H, H(4),
Ar, J = 8.1 Hz, J = 7.8 Hz, J = 1.2 Hz); 7.82 (ddd, 1 H, H(5), Ar,
J = 7.8 Hz, J = 7.8 Hz, J = 1.0 Hz); 8.18 (dd, 1 H, H(3), Ar,
J = 8.1 Hz, J = 1.0 Hz).
3ꢀArylꢀ3ꢀbromoꢀ2ꢀhydroxypropionamides (2a—e) were obꢀ
tained similarly to the procedure described earlier19 for anilides
of this acid in dioxane as a solvent. synꢀDiastereomers crystalꢀ
lized in the reaction mixture within 1 h. The products were
filtered, washed with water, and dried. Diastereomers antiꢀ2a—c
were isolated from the water—dioxane filtrates after 24 h.
synꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀphenylpropionamide (synꢀ2a).
M.p. 145—146 °C. Found (%): C, 44.38; H, 4.01; Br, 32.31; N, 5.35.
C9H10BrNO2. Calculated (%): C, 44.29; H, 4.13; Br, 32.74;
N, 5.74. IR, ν/cm–1: 1656 (C=O), 3186, 3381 (OH, C(O)NH2).
1H NMR, δ: 4.42, 5.37 (both d, 1 H each, H(2), H(3), J = 5.7 Hz);
7.17, 7.37 (both br.s, 1 H each, NH2); 7.23—7.50 (m, 5 H, Рh).
antiꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀphenylpropionamide (antiꢀ2a).
M.p. 146—147 °C. Found (%): C, 44.21; H, 4.02; Br, 32.70;
N, 5.79. C9H10BrNO2. Calculated (%): C, 44.29; H, 4.13; Br, 32.74;
N, 5.74. IR, ν/cm–1: 1682 (C=O), 3187, 3334, 3435 (OH,
C(O)NH2). 1H NMR, δ: 4.14, 5.49 (both d, 1 H each, H(2) and
H(3), J = 2.8 Hz); 7.26—7.55 (m, 7 H, Рh, NH2).
(both d, 1 H each, H(2) and H(3), J = 5.7 Hz); 6.85 (dd, 1 H,
H(4), Ar, J = 8.1 Hz, J= 1.7 Hz); 7.03 (d, 1 H, H(6), Ar, J = 7.9 Hz);
7.04 (s, 1 H, H(2), Ar); 7.19, 7.39 (both br.s, 1 H each, NH2);
7.22 (dd, 1 H, H(5), Ar, J = 8.1 Hz, J = 7.9 Hz).
antiꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀ(3ꢀmethoxyphenyl)propionamide
(antiꢀ2c). M.p. 129—130 °C. Found (%): C, 43.89; H, 4.32;
Br, 29.28; N, 5.18. C10H12BrNO3. Calculated (%): C, 43.82;
H, 4.41; Br, 29.15; N, 5.11. IR, ν/cm–1: 1651 (C=O), 3289, 3385
(OH, C(O)NH2). 1H NMR, δ: 3.55 (s, 3 H, OMe); 4.14, 5.46
(both d, 1 H each, H(2) and H(3), J = 2.9 Hz); 6.87 (dd, 1 H,
H(4), Ar, J = 8.1 Hz, J= 1.9 Hz); 7.10 (d, 1 H, H(6), Ar, J = 8.1 Hz);
7.13 (s, 1 H, H(2), Ar); 7.25 (dd, 1 H, H(5), Ar, J = 8.1 Hz);
7.33, 7.41 (both br.s, 1 H each, NH2).
synꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀ(4ꢀtrifluoromethylphenyl)proꢀ
pionamide (synꢀ2d). M.p. 144—145 °C. Found (%): C, 38.38;
H, 2.89; Br, 25.66; F, 18.21; N, 4.52. C10H9BrF3NO2. Calculatꢀ
ed (%): C, 38.49; H, 2.91; Br, 25.60; F, 18.26; N, 4.49. IR,
ν/cm–1: 1665 (C=O), 3189, 3396 (OH, C(O)NH2). 1H NMR, δ:
4.43, 5.44 (both d, 1 H each, H(2) and H(3), J = 5.2 Hz); 7.19,
7.38 (both br.s, 1 H each, NH2); 7.60—7.70 (m, Ar).
synꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀ(2ꢀnitrophenyl)propionamide
(synꢀ2e). M.p. 167—168 °C. Found (%): C, 37.56; H, 3.12;
Br, 27.58; N, 9.72. C9H9BrN2O4. Calculated (%): C, 37.39;
H, 3.14; Br, 27.64; N, 9.69. IR, ν/cm–1: 1524 (NO2), 1681 (C=O),
3317, 3441 (OH, C(O)NH2). 1H NMR, δ: 4.48, 5.79 (both d,
1 H each, H(2) and H(3), J = 6.6 Hz); 7.23, 7.50 (both br.s,
1 H each, NH2); 7.54 (dd, 1 H, H(5), Ar, J = 8.2 Hz, J = 7.7 Hz);
7.71 (dd, 1 H, H(4), Ar, J = 7.2 Hz); 7.83 (d, 1 H, H(6), Ar,
J = 8.2 Hz); 7.99 (d, 1 H, H(3), Ar, J = 7.7 Hz).
Synthesis of 5ꢀ[bromo(aryl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazoꢀ
lidinꢀ4ꢀones (3a—e). A. A 47% aqueous HBr (10 mL) was added
to a solution of Eꢀ3ꢀarylꢀ2,3ꢀepoxypropionamide 1 (1 mmol) in
acetone (10 mL). The solution was allowed to stand at room
temperature for 24 h and poured into water (20 mL). A precipiꢀ
tate formed within 1 h was filtered, washed with water, and dried
in air. This procedure was used to obtain synꢀ3d (0.35 g, 99%)
and synꢀ3e (0.32 g, 98%). The product synꢀ3a (0.04 g, 14%)) was
isolated from the water—acetone mixture after 15 min. The next
portion of the precipitate collected after 1 h was a 3 : 1 mixture of
synꢀ3a and antiꢀ3a (0.13 g, 46%). A precipitate formed after 24 h
corresponded to antiꢀ3a (0.10 g, 36%).
B. A solution of the corresponding amide 2a—e (1 mmol) in
acetone (10 mL) and concentrated H2SO4 (0.1 mL) was allowed
to stand for 24 h at room temperature and poured into water
(30 mL). A precipitate formed was filtered, washed with water,
and dried in air. The yields of obtained products 3 are given
in Table 3.
synꢀ3ꢀBromoꢀ3ꢀ(4ꢀbromophenyl)ꢀ2ꢀhydroxypropionamide
(synꢀ2b). M.p. 150—151 °C. Found (%): C, 33.58; H, 2.78;
Br, 49.35, N, 4.50. C9H9Br2NO2. Calculated (%): C, 33.47;
H, 2.81; Br, 49.48; N, 4.34. IR, ν/cm–1: 1673 (C=O), 3140, 3341,
3442 (OH, C(O)NH2). 1H NMR, δ: 4.39, 5.37 (both d, 1 H each,
H(2) and H(3), J = 5.2 Hz); 7.18, 7.35 (both br.s, 1 H each,
NH2); 7.41, 7.49 (both d, 2 H each, Ar, J = 8.1 Hz).
Characteristics of the same compounds obtained by alternaꢀ
tive procedures were identical.
antiꢀ3ꢀBromoꢀ3ꢀ(4ꢀbromophenyl)ꢀ2ꢀhydroxypropionamide
(antiꢀ2b). M.p. 149—150 °C. Found (%): C, 33.25; H, 2.58;
Br, 49.29; N, 4.38. C9H9Br2NO2. Calculated (%): C, 33.47;
H, 2.81; Br, 49.48; N, 4.34. IR, ν/cm–1: 1689 (C=O), 3283, 3375
(OH, C(O)NH2). 1H NMR, δ: 4.11, 5.48 (both d, 1 H each,
H(2) and H(3), J = 2.9 Hz); 7.35, 7.41 (both br.s, 1 H each,
NH2); 7.49, 7.52 (both d, 2 H each, Ar, J = 8.1 Hz).
synꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀ(3ꢀmethoxyphenyl)propionamide
(synꢀ2c). M.p. 123—124 °C. Found (%): C, 43.57; H, 4.38;
Br, 28.95; N, 5.15. C10H12BrNO3. Calculated (%): C, 43.82;
H, 4.41; Br, 29.15; N, 5.11. IR, ν/cm–1: 1662 (C=O), 3189, 3375
(OH, C(O)NH2). 1H NMR, δ: 3.74 (s, 3 H, OMe); 4.41, 5.33
synꢀ5ꢀ[Bromo(phenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ
4ꢀone (synꢀ3a). M.p. 192—194 °C. Found (%): C, 50.53; H, 5.02;
Br, 28.27; N, 4.91. C12H14BrNO2. Calculated (%): C, 50.72;
H, 4.97; Br, 28.12; N, 4.93. IR, ν/cm–1: 1684, 1722 (C=O), 3437
(C(O)NH). 1H NMR, δ: 1.12, 1.34 (both s, 3 H each, 2 Me);
4.83, 5.41 (both d, 1 H each, 2 CH, J = 3.0 Hz); 7.26—7.32 (m, 3 H,
H(3), H(4) and H(5), Рh); 7.51 (d, 2 H, H(2) and H(6), Ph,
J = 6.6 Hz); 8.95 (br.s, 1 H, NH).
antiꢀ5ꢀ[Bromo(phenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ
4ꢀone (antiꢀ3a). M.p. 148—149 °C. Found (%): C, 50.90; H, 4.98;
Br, 28.18, N, 4.79. C12H14BrNO2. Calculated (%): C, 50.72;
H, 4.97; Br, 28.12; N, 4.93. IR, ν/cm–1: 1710 (C=O), 3213,

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Mamedov et al.
3265 (C(O)NH). 1H NMR, δ: 1.41, 1.55 (both s, 3 H each,
2 Me); 4.63, 5.44 (both d, 1 H each, 2 CH, J = 1.7 Hz); 7.28—7.33
(m, 3 H, H(3), H(4) and H(5), Рh); 7.57 (d, 2 H, H(2) and H(6),
Ph, J = 7.2 Hz); 9.18 (br.s, 1 H, NH).
synꢀ5ꢀ[Bromo(4ꢀbromophenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxꢀ
azolidinꢀ4ꢀone (synꢀ3b). M.p. 181—182 °C. Found (%): C, 39.67;
H, 3.58; Br, 44.13; N, 3.92. C12H13Br2NO2. Calculated (%):
C, 39.70; H, 3.61; Br, 44.02; N, 3.86. IR, ν/cm–1: 1707 (C=O),
3189 (C(O)NH). 1H NMR, δ: 1.16, 1.34 (both s, 3 H each,
2 Me); 4.81, 5.42 (both d, 1 H each, 2 CH, J = 2.8 Hz); 7.47, 7.52
(both d, 2 H each, Ar, J = 8.6 Hz); 8.99 (s, 1 H, NH).
antiꢀ5ꢀ[Bromo(4ꢀbromophenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀ
oxazolidinꢀ4ꢀone (antiꢀ3b). M.p. 147—149 °C. Found (%): C, 39.
67; H, 3.65; Br, 44.24; N, 3.88. C12H13Br2NO2. Calculated (%):
C, 39.70; H, 3.61; Br, 44.02; N, 3.86. IR, ν/cm–1: 1711 (C=O),
3173 (C(O)NH). 1H NMR, δ: 1.40, 1.54 (both s, 3 H each,
2 Me); 4.63, 5.46 (both d, 1 H each, 2 CH, J = 1.9 Hz); 7.53
(d, 4 H, Ar, J = 7.7 Hz); 9.20 (br.s, 1 H, NH).
C12H13NO2. Calculated (%): C, 70.92; H, 6.45; N, 6.89. IR,
ν/cm–1: 1671 (C=C), 1703 (C=O), 3026, 3161 (C(O)NH).
1H NMR, δ: 1.53 (s, 6 H, 2 Me); 6.04 (s, 1 H, =CH); 7.22 (dd,
1 H, H(4), Рh, J = 7.5 Hz); 7.34 (dd, 2 H, H(3) and H(5), Рh,
J = 7.5 Hz); 7.64 (d, 2 H, H(2) and H(6), Рh, J = 7.5 Hz); 9.76
(br.s, 1 H, NH).
(E)ꢀ5ꢀBenzylideneꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀone (Eꢀ4a)
was obtained in the mixture with Zꢀ4a (the ratio Eꢀ4a : Zꢀ4a = 4 : 1).
1H NMR, δ: 1.46 (s, 6 H, 2 Me); 6.20 (s, 1 H, =CH); 7.17 (dd,
1 H, H(4), Рh, J = 7.6 Hz); 7.26 (dd, 2 H, H(3) and H(5); Рh,
J = 7.6 Hz); 7.78 (d, 2 H, H(2) and H(6), Рh, J = 7.6 Hz); 9.64
(br.s, 1 H, NH).
(E)ꢀ5ꢀ(4ꢀBromobenzylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀ
one (Eꢀ4b). M.p. 143—144 °C. Found (%): C, 49.92; H, 4.28;
Br, 28.28; N, 5.02. C12H12BrNO2. Calculated (%): C, 51.08,
H, 4.30, N, 4.97, Br, 28.32. IR, ν/cm–1: 1655 (C=C), 1705 (C=O),
3049, 3160 (C(O)NH). 1H NMR, δ: 1.48 (s, 6 H, 2 Me); 6.18
(s, 1 H, =CH); 7.45, 7.77 (both d, 2 H each, Ar, J = 8.4 Hz).
(Z)ꢀ5ꢀ(3ꢀMethoxybenzylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ
4ꢀone (Zꢀ4c). M.p. 145—146 °C. Found (%): C, 66.83; H, 6.51;
N, 6.18. C13H15NO3. Calculated (%): C, 66.94; H, 6.48; N, 6.00.
IR, ν/cm–1: 1682 (C=C), 1714 (C=O), 3017, 3160 (C(O)NH).
1H NMR, δ: 1.54 (s, 6 H, 2 Me); 3.76 (s, 3 H, OMe); 6.00 (s, 1 H,
=CH); 6.83 (dd, 1 H, H(4), Ar, J = 8.1 Hz, J = 1.8 Hz); 7.21
(s, 1 H, H(2), Ar); 7.22 (d, 1 H, H(6), Ar, J = 7.6 Hz); 7.27 (dd,
1 H, H(5), Ar, J = 8.1 Hz, J = 7.6 Hz); 9.66 (br.s, 1 H, NH).
(E)ꢀ2,2ꢀDimethylꢀ5ꢀ(3ꢀmethoxybenzylidene)ꢀ1,3ꢀoxazolidinꢀ
4ꢀone (Eꢀ4c). M.p. 151—152 °C. Found (%): C, 66.82; H, 6. 45;
N, 6.15. C13H15NO3. Calculated (%): C, 66.94; H, 6.48; N, 6.00.
IR, ν/cm–1: 1650 (C=C), 1707 (C=O), 3081, 3215 (C(O)NH).
1H NMR, δ: 1.48 (s, 6 H, 2 Me); 6.18 (s, 1 H, =CH); 6.76 (dd,
1 H, H(4), Ar, J = 8.1 Hz, J = 2.5 Hz); 7.18 (dd, 1 H, H(5), Ar,
J = 7.8 Hz, J = 8.1 Hz); 7.28 (d, 1 H, H(6), Ar, J = 7.8 Hz); 7.66
(s, 1 H, H(2), Ar); 9.63 (br.s, 1 H, NH).
(E)ꢀ2,2ꢀDimethylꢀ5ꢀ(4ꢀtrifluoromethylbenzylidene)ꢀ1,3ꢀoxꢀ
azolidinꢀ4ꢀone (Eꢀ4d). M.p. 179 °C. Found (%): C, 57.38;
H, 4.42; F, 21.25; N, 5.18. C13H12F3NO2. Calculated (%): C, 57.57;
H, 4.46; F, 21.01; N, 5.16. IR, ν/cm–1: 1714 (C=O), 3057, 3171
(C(O)NH). 1H NMR, δ: 1.49 (s, 6 H, 2 Me); 6.28 (s, 1 H, =CH);
7.61, 7.99 (both d, 2 H each, Ar, J = 8.1 Hz); 9.81 (br.s, 1 H, NH).
(E)ꢀ2,2ꢀDimethylꢀ5ꢀ(2ꢀnitrobenzylidene)ꢀ1,3ꢀoxazolidinꢀ4ꢀ
one (Eꢀ4e). M.p. 189—90 °C. Found (%): C, 57.91; H, 4.88;
N, 11.32. C12H12N2O4. Calculated (%): C, 58.06; H, 4.87;
N, 11.29. IR, ν/cm–1: 1520 (NO2), 1692 (C=C), 1706 (C=O), 3095,
3274 (C(O)NH). 1H NMR, δ: 1.54 (s, 6 H, 2 Me); 6.27 (s, 1 H,
=CH); 7.45, 7.69 (both dd, 1 H each, H(4) and H(5), Ar, J= 7.3 Hz);
7.91, 8.07 (both d, 1 H each, H(3) and H(6), Ar, J = 7.5 Hz);
9.95 (br.s, 1 H, NH).
synꢀ5ꢀ[Bromo(3ꢀmethoxyphenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀ
oxazolidinꢀ4ꢀone (synꢀ3c). M.p. 135—136 °C. C13H16BrNO3.
Found (%): C, 49.79; H, 5.12; Br, 25.03; N, 4.48. C13H16BrNO3.
Calculated (%): C, 49.70; H, 5.13; Br, 25.43; N, 4.46. IR, ν/cm–1
:
1683, 1726 (C=O), 3218 (C(O)NH). 1H NMR, δ: 1.16, 1.35 (both s,
3 H each, 2 Me); 3.73 (s, 3 H, OMe); 4.82, 5.38 (both d, 1 H each,
2 CH, J = 2.6 Hz); 6.87 (dd, 1 H, H(4), Ar, J = 8.1 Hz, J = 1.9 Hz);
7.08 (d, 1 H, H(6), Ar, J = 8.6 Hz); 7.13 (s, 1 H, H(2); Ar); 7.23
(dd, 1 H, H(5), Ar, J = 8.1 Hz, J = 8.6 Hz); 8.97 (s, 1 H, NH).
antiꢀ5ꢀ[Bromo(3ꢀmethoxyphenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀ
oxazolidinꢀ4ꢀone (antiꢀ3c). M.p. 153—154 °C. Found (%):
C, 49.58; H, 5.11; Br, 25.38; N, 4.49. C13H16BrNO3. Calculatꢀ
ed (%): C, 49.70; H, 5.13; Br, 25.43; N, 4.46. IR, ν/cm–1: 1715
(C=O), 3164 (C(O)NH). 1H NMR, δ: 1.39, 1.53 (both s, 3 H each,
2 Me); 4.59, 5.38 (both br.s, 1 H each, 2 CH); 6.87 (d, 1 H, H(4),
Ar, J = 8.1 Hz); 7.11 (s, 1 H, H(2), Ar); 7.12 (d, 1 H, H(6), Ar,
J = 7.6 Hz); 7.25 (dd, 1 H, H(5), Ar, J = 8.1 Hz, J = 7.6 Hz);
9.18 (br.s, 1 H, NH).
synꢀ5ꢀ[Bromo(2ꢀtrifluoromethylphenyl)methyl]ꢀ2,2ꢀdimethꢀ
ylꢀ1,3ꢀoxazolidinꢀ4ꢀone (synꢀ3d). M.p. 158—159 °C. Found (%):
C, 44.42; H, 3.73; Br, 22.58; F, 16.25; N, 4.01. C13H13BrF3NO2.
Calculated (%): C, 44.34; H, 3.72; Br, 22.69; F, 16.19; N, 3.98.
1
IR, ν/cm–1: 1711 (C=O), 3079, 3175 (C(O)NH). H NMR, δ:
1.14, 1.35 (both s, 3 H each, 2 Me); 4.87, 5.53 (both d, 1 H each,
2 CH, J = 2.4 Hz); 7.69, 7.74 (both d, 2 H each, Ar, J = 8.2 Hz);
9.02 (s, 1 H, NH).
synꢀ5ꢀ[Bromo(2ꢀnitrophenyl)methyl]ꢀ2,2ꢀdimethylꢀ1,3ꢀoxꢀ
azolidinꢀ4ꢀone (synꢀ3e). M.p. 164—155 °C. Found (%): C, 43.57;
H, 3.93; Br, 24.21; N, 8.58. C12H13BrN2O4. Calculated (%):
C, 43.79; H, 3.98; Br, 24.28; N, 8.51. IR, ν/cm–1: 1597 (NO2),
1682, 1719 (C=O), 3170, 3426 (C(O)NH). 1H NMR, δ: 1.28,
1.36 (both s, 3 H each, 2 Me); 4.93, 5.86 (both d, 1 H each,
2 CH, J = 3.0 Hz); 7.58 (dd, 1 H, H(4), Ar, J = 7.2 Hz); 7.75
(dd, 1 H, H(5), Ar, J = 7.2 Hz, J = 7.7 Hz); 7.87 (d, 1 H,
H(6), Ar, J = 7.7 Hz); 8.13 (d, 1 H, H(3), Ar, J = 7.2 Hz); 9.08
(s, 1 H, NH).
This work was financially supported by the Russian
Science Foundation (Priority Area of Studies "Fundamental
Scientific Studies and Scientific Search by the Personal of
Existing Research Laboratories (Departments)" (Project
No. 14ꢀ23ꢀ00073)).
Synthesis of 5ꢀ(arylmethylidene)ꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolꢀ
idinꢀ4ꢀones (4a—e) (general procedure). The salt K2CO3 (0.41 g,
3 mmol) and MeOH (15 mL) were added to compound 3
(1 mmol). The mixture was stirred at room temperature for 3 h,
poured into water (30 mL), and allowed to stand for 12 h.
A precipitate formed was filtered, washed with water, and dried in air.
(Z)ꢀ5ꢀBenzylideneꢀ2,2ꢀdimethylꢀ1,3ꢀoxazolidinꢀ4ꢀone (Zꢀ4a).
M.p. 157—158 °C. Found (%): C, 70.81; H, 6.46; N, 6.82.
References
1. V. G. Granik, Lekarctva [Medicines], Vuzovskaya kniga,
Moscow, 2001, 407 pp. (in Russian).
2. M. D. Mashkovskii, Lekarstvennye sredstva [Medicinal
Drugs], Novaya volna, Moscow, 2007, 1206 pp. (in Russian).

1,3ꢀOxazolidinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 5, May, 2016
1267
3. S. J. Brickner, D. R. Hutchinson, M. R. Barbachyn, P. R.
Manninen, D. A. Ulanowicz, S. A. Garmon, K. C. Grega,
S. K. Hendges, D. S. Toops, C. W. Ford, G. E. Zurenko,
J. Med. Chem., 1996, 39, 673.
4. F. Tomita, K. Takahashi, T. Tamaoki, J. Antibiot., 1984,
37, 1268.
14. W. R. Roush, A. P. Essenfeld, J. S. Warmus, B. B. Brown,
Tetrahedron Lett., 1989, 30, 7305.
15. S. Cesa, V. Mucciante, L. Rossi, Tetrahedron, 1999, 55, 193.
16. V. A. Mamedov, V. L. Mamedova, S. F. Kadyrova, G. Z.
Khikmatova, A. T. Gubaidullin, I. Kh. Rizvanov, Sh. K.
Latypov, Tetrahedron, 2015, 71, 2670.
5. T. Ooi, K. Fukumoto, K. Maruoka, Angew. Chem., Int. Ed.,
2006, 45, 3839.
6. P.ꢀL. Shao, X.ꢀY. Chen, S. Ye, Angew. Chem., Int. Ed., 2010,
49, 8412.
7. G. Cardillo, M. A. Hashem, C. Tomasini, J. Chem. Soc.,
Perkin Trans. 1, 1990, 1487.
8. Y. Numajiri, G. JimenezꢀOses, B. Wang, K. N. Houk, B. M.
Stoltz, Org. Lett., 2015, 17, 1082.
9. G. M. Coppola, H. F. Schuster, αꢀHydroxy Acids in Enantioꢀ
selective Synthesis, VCH, Weinheim, 1997.
10. J. W. Cornforth, in Heterocyclic Compounds, Ed. R. C. Elderꢀ
field, Wiley, New York, 1957, Vol. 5, pp. 298, 402.
11. J. B. Bicking, S. F. Kwong, M. H. Fleischer, W. H. Nicholꢀ
son, J. Med. Chem., 1965, 8, 95.
12. I. I. Lapkin, N. A. Samoilovskikh, L. M. Mikryukova,
Zh. Org. Khim. [J. Org. Chem. USSR], 1974, 10, 1769
(in Russian).
17. E. Fourneau, J. R. Billeter, Bull. Soc. Chim. Fr., 1940, 7, 593.
18. J. Baldas, Q. N. Porter, Aust. J. Chem., 1967, 20, 2655.
19. V. A. Mamedov, V. L. Mamedova, G. Z. Khikmatova, A. I.
Samigullina, A. T. Gubaidullin, O. B. Bazanova, I. Kh. Rizꢀ
vanov, O. G. Sinyashin, Russ. Chem. Bull. (Int. Ed.), 2015,
64, 2857 [Izv. Akad. Nauk, Ser. Khim., 2015, 2857].
20. G. M. Sheldrick, SADABS, Program for Empirical Xꢀray
Absorption Correction, BrukerꢀNonius, 1990—2004.
21. G. M. Sheldrick, SHELXLꢀ97, Program for Cristal Structure
Refinement, University of Goettingen, Goettingen, Germany,
1997.
22. L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
23. APEX2 (Version 2.1), SAINTPlus. Data Reduction and Correcꢀ
tion Program (Version 7.31A), Bruker Advansed Xꢀray Soluꢀ
tions, Inc., Madison (WI), 2006.
Received November 19, 2015;
in revised form March 29, 2016
13. T. Pokonski, Tetrahedron, 1983, 39, 3139.