Synthesis of substituted 2-(2-oxopyrrolidin-1-yl)acetamides

Article abstract of DOI:10.1134/S1070428017060100

The reaction of chloroacetamide with 2 equiv of γ-aminobutyric acid potassium salts provides a convenient method for the synthesis of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids. Alkylation products of 2-aminoacetic and 3-aminopropanoic acid with chloroacetamide were isolated. Thermal cyclization of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids afforded 2-(2-oxopyrrolidin-1-yl)acetamides.

Full text of DOI:10.1134/S1070428017060100

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 6, pp. 873–878. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © M.A. Kavina, V.V. Sizov, I.P. Yakovlev, 2017, published in Zhurnal Organicheskoi Khimii, 2017, Vol. 53, No. 6, pp. 857–862.
Synthesis of Substituted 2-(2-Oxopyrrolidin-1-yl)acetamides
M. A. Kavinaa, b, V. V. Sizova,* and I. P. Yakovlevb
a CHEM Ltd. Scientific and Production Company,
ul. Zavodskaya 3, bld. 142, Kuz’molovskii, Leningrad oblast, 188663 Russia
*e-mail: vvsizov@list.ru
b St. Petersburg State Chemical Pharmaceutical Academy,
ul. Prof. Popova 14, St. Petersburg, 197022 Russia
Received March 17, 2017
Abstract—The reaction of chloroacetamide with 2 equiv of γ-aminobutyric acid potassium salts provides
a convenient method for the synthesis of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids. Alkylation
products of 2-aminoacetic and 3-aminopropanoic acid with chloroacetamide were isolated. Thermal cyclization
of substituted 4-[(2-amino-2-oxoethyl)amino]butanoic acids afforded 2-(2-oxopyrrolidin-1-yl)acetamides.
DOI: 10.1134/S1070428017060100
2-(2-Oxopyrrolidin-1-yl)acetamide derivatives are
known as biologically active compounds exhibiting
psychotropic and cerebroprotective effects [1]. Medici-
nals based on 2-(2-oxopyrrolidin-1-yl)acetamide are
widely used for the treatment of central nervous
system and cerebrovascular disorders [2]. Among
these, the most widely known are 2-(2-oxopyrrolidin-
1-yl)acetamide (Piracetam) and 2-(2-oxo-4-phenylpyr-
rolidin-1-yl)acetamide (Phenylpiracetam) which have
been discovered in the second half of the XXth century
[3, 4]. Interest in 2-(2-oxopyrrolidin-1-yl)acetamide
derivatives has continued until now, and development
of new efficient laboratory and large-scale procedures
for the synthesis of substituted 2-(2-oxopyrrolidin-1-
yl)acetamide is a topical problem.
have some essential drawbacks, the main of which is
difficult isolation of the target compounds. Therefore,
special methods are necessary for purification of the
products, which reduces the efficiency of the synthesis.
In this work, the alkylation of 3-substituted
4-aminobutanic acids 1a–1g with chloroacetamide (2)
was carried out by preliminarily converting acids 1 to
potassium salts in aliphatic alcohols (methanol,
ethanol, propan-2-ol, or their mixtures), adding
0.5 equiv of chloroacetamide (2), and heating the reac-
tion mixture at 65–75°C for 3–4 h. After cooling and
removal of unreacted acid 1 and potassium chloride by
filtration, acidification of the filtrate with acetic acid
afforded pure 3-substituted 4-[(2-amino-2-oxoethyl)-
amino]butanoic acids 3a–3g whose subsequent thermal
cyclization in a high-boiling solvent (anisole or
o-xylene) gave 2-(2-oxopyrrolidin-1-yl)acetamides
4a–4g (Scheme 1).
The use of sodium hydroxide was inappropriate
since 4-aminobutanoic acid sodium salts are poorly
soluble in alcohols. The solvent and its amount were
selected taking into account the solubility of the initial
compounds, target products, and by-products. Excess
potassium salt of acid 1 with respect to 2 (ratio 1:2 ≥
2:1) was taken for the following reasons. It is known
that alkylation of amino acids may be accompanied by
formation of N,N- and N,O-dialkyl derivatives (in our
case, compounds 5 and 6). 4-Aminobutanoic acid
esters with aliphatic alcohols were reported to undergo
intramolecular cyclization to pyrrolidinones [13, 14].
Known methods for the synthesis of 2-(2-oxopyrro-
lidin-1-yl)acetamide derivatives are generally based on
the alkylation of pyrrolidin-2-ones with haloacetic acid
esters in the presence of sodium hydride, metal alkox-
ides, or lithium diisopropylamine, as well as of tri-
methylsilyl derivatives, followed by ammonolysis
[5–11]. An alternative method is intramolecular acyla-
tion of N-substituted 4-aminobutanoic acid esters pre-
pared by condensation of 4-halobutanoyl chlorides
with glycine esters [12] or 2-aminobutanamides [13].
The alkylation of 4-aminobutanoic acids with haloacet-
amides has been reported. The resulting N-substituted
4-aminobutanoic acid esters were converted to
2-(2-oxopyrrolidin-1-yl)acetamides by thermal cy-
clization in organic solvents [13, 14]. These procedures
873

KAVINA et al.
874
Scheme 1.
O
(1) KOH (2 equiv)
(2) AcOH
R1
R2
O
O
O
O
O
R1
R2
R1
R2
∆
H
2
+
H2N
Cl
N
N
OH
NH2
H2N
OH
H2N
4a–4g
1a–1g
2
3a–3g
2
O
NH2
N
O
O
R1
R2
OH
H
N
NH2
H2N
O
O
Ph
O
O
NH2
5b
6
R1 = H, R2 = H (a), Ph (b), 2,4-Cl2C6H3 (c), 4-ClC6H4 (d), 4-MeOC6H4 (e), 3-O2NC6H4 (f); R1R2 = (CH2)5 (g).
withdrawn and frozen with dry ice. Samples were then
analyzed by HPLC/MS according to a developed pro-
cedure. Figure shows variations of the concentrations
of the initial compounds and products with time at
different temperatures.
Obviously, cyclization of 6 in alcohol at 26–65°C
yields 2-(2-oxopyrrolidin-1-yl)acetamides 4, as fol-
lows from the HPLC/MS data.
Thus, excess potassium salt partially suppresses
side formation of compounds 5 and 6 and acts as
a base which neutralizes liberated hydrogen chloride.
As a result, initial amino acid 1 is formed. It is poorly
soluble in alcohols and precipitates from the reaction
mixture. After purification from potassium chloride, it
can be reused. Acid 3 is also poorly soluble in alcohol
and is precipitated by acidification with acetic acid,
whereas by-product 5 and compound 4 arising from
N,O-bis(2-amino-2-oxoethyl) derivative 6 remain in
solution.
Most part of initial amino acid 1b is converted to
3b during the first hour at 65°C, and then the rate of
alkylation sharply decreases. After 3 h, the fraction of
3b begins to decrease due to formation of by-products,
while the concentrations of 5b and 4b increase.
Lowering the temperature to 45°C reduces the reaction
rate, so that the time necessary to achieve the maxi-
mum concentration of 3b increases to 14 h. The corre-
sponding time at 26°C is 55 h.
The kinetics of the formation of 4-[(2-amino-2-oxo-
ethyl)amino]-3-phenylbutanoic acid (3b) were studied
as follows. The reaction mixture was kept for different
periods of time (15 min to 168 h) at a specified tem-
perature (26, 45, or 65°C) and diluted with a 10-fold
volume of cold distilled water. The resulting mixture
was filtered, and a 1-mL sample of the filtrate was
The reaction selectivity depends on the temperature
conditions. At 26°C, compound 3b is consumed
mainly for the formation of N,N-disubstituted deriva-
tive 5b, whereas raising the temperature to 65°C favors
formation of pyrrolidone 4b, which indicates preva-
lence of O-alkylation. The yields of 3-substituted
4-[(2-amino-2-oxoethyl)amino]butanoic acids 3 were
Scheme 2.
(1) KOH (2 equiv), MeOH
(2) AcOH
O
O
O
O
H
N
2
+ 2
H2N
OH
OH
H2N
H2N
OH
O
7
8
(1) KOH (2 equiv), EtOH
(2) AcOH
2
+ 2
N
H
OH
H2N
O
9
10
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SYNTHESIS OF SUBSTITUTED 2-(2-OXOPYRROLIDIN-1-YL)ACETAMIDES
875
c, mg/mL
(a)
c, mg/mL
(b)
10.0
8.0
6.0
4.0
2.0
10.0
8.0
6.0
4.0
2.0
0.0
0.0
0
20
40
60
80
100 120 140 160
0
2
4
6
8
10 12 14 16 18 20 22 24
Time, h
Time, h
c, mg/mL
(c)
10.0
8.0
6.0
4.0
2.0
0.0
0
40
80 120 160 200 240 280 320 360
Time, h
Variation of the concentrations of the initial compounds and products in the reaction mixture during the reaction of 4-amino-3-
phenylbutanoic acid (1b) with chloroacetamide (2) at (a) 26, (b) 45, and (c) 65°C.
50–80%, and of the cyclization products, 2-(2-oxopyr-
rolidin-1-yl)acetamides 4, 70–97%.
phenylbutanoic acid and qualitative and quantitative
compositions of the products were found to depend on
the reaction conditions (temperature and time), and
optimal conditions were determined. N-(2-Amino-2-
oxoethyl) derivatives of substituted 4-aminobutanoic
acids and its nearest homolog, 3-aminopropanoic acid,
were isolated for the first time. The structure of the
In order to extend the scope of the described reac-
tion, chloroacetamide was reacted with aminoacetic
acid (7) and 3-aminopropanoic acid (9) that are homo-
logous to 4-aminobutanoic acid. As a result, [(2-amino-
2-oxoethyl)amino]acetic acid (8) and 3-[(2-amino-2-
oxoethyl)amino]propanoic acid (10) were obtained in
50 and 70% yield, respectively (Scheme 2).
1
isolated compounds was confirmed by H and 13C
NMR spectra and elemental analyses.
In summary, substituted 2-(2-oxopyrrolidin-1-yl)-
acetamides can readily be synthesized according to the
proposed procedure which is suitable not only for
laboratory but also for large-scale applications. The
rate of formation of 4-[(2-amino-2-oxoethyl)amino]-3-
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
a Bruker Avance III UltraShield Plus spectrometer
(400 MHz). HPLC/MS analyses were done with
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 6 2017

KAVINA et al.
876
a Thermo Fisher Scientific TSQ Quantum Access
MAX instrument [Zorbax SB-18 column, 150 ×
2.10 mm, grain size 1.8 μm; column temperature 35°C;
sample compartment temperature 5°C; eluents 0.1%
aqueous formic acid (for HPLC) and acetonitrile (for
gradient HPLC); gradient elution]. Detailed procedure
for studying the kinetics of formation of compound 3b
is available from the authors by e-mail. The elemental
analyses were obtained using a Thermo Scientific
FLASH 2000 CHNS analyzer. The melting points were
measured on a melting point apparatus equipped with
an electric heater (measurement range 20–360°C).
δ, ppm: 2.50–2.65 m (2H, CH2), 3.34 d (2H, CH2, J =
4.0 Hz), 3.82 s (2H, CH2), 3.94 quint (1H, CH, J =
8.0 Hz), 7.30–7.36 m (2H, Harom), 7.51 s (1H, Harom).
Found, %: C 47.15; H 4.56; N 9.11. C12H14Cl2N2O3.
Calculated, %: C 47.23; H 4.62; N 9.18.
4-[(2-Amino-2-oxoethyl)amino]-3-(4-chlorophe-
nyl)butanoic acid (3d). Solvent ethanol. Yield 52–
53%, colorless prisms, mp 142.5–144.5°C (decomp.,
from MeOH). 1H NMR spectrum (D2O), δ, ppm: 2.39–
2.56 m (2H, CH2), 3.27–3.39 m (3H, CH2, CH), 3.70–
3.79 m (2H, CH2), 7.23 d (2H, Harom, J = 6.0 Hz),
7.34 d (2H, Harom, J = 6.0 Hz). Found, %: C 53.18;
H 5.49; N 10.28. C12H15ClN2O3. Calculated, %:
C 53.24; H 5.58; N 10.35.
Compounds 3a–3f (general procedure). Amino
acid 1a–1f, 1 mol, was added to a solution of 1 mol
of potassium hydroxide in ethanol or ethanol–propan-
2-ol (2:1) (8 mL per gram of amino acid), and the
mixture was heated to 65–75°C and stirred until com-
plete dissolution. Chloroacetamide, 0.5 mol, was added
to the resulting solution, the mixture was stirred for
3–4 h at 65–75°C and cooled to room temperature, and
the precipitate of potassium chloride and initial amino
acid was filtered off and washed with alcohol. The
filtrate was acidified with glacial acetic acid (0.5 mol),
the mixture was stirred until complete crystallization,
and the precipitate was filtered off, washed with alco-
hol, and dried at a temperature not higher than 75°C.
4-[(2-Amino-2-oxoethyl)amino]-3-(4-methoxy-
phenyl)butanoic acid (3e). Solvent ethanol–propan-2-
ol (2:1). Yield 68–70%, colorless prisms, mp 137–
1
140°C (decomp., from MeOH). H NMR spectrum
(D2O), δ, ppm: 2.40–2.56 m (2H, CH2), 3.24–3.38 m
(3H, CH2, CH), 3.71–3.80 m (2H, CH2), 3.76 s (3H,
CH3), 6.95 d (2H, Harom, J = 4.0 Hz), 7.24 d (2H, Harom
,
J = 4.0 Hz). Found, %: C 58.54; H 6.74; N 10.46.
C13H18N2O4. Calculated, %: C 58.63; H 6.81; N 10.52.
4-[(2-Amino-2-oxoethyl)amino]-3-(3-nitrophe-
nyl)butanoic acid (3f). Solvent ethanol–propan-2-ol
(2:1). Yield 69–71%, light brown prisms, mp 151–
1
4-[(2-Amino-2-oxoethyl)amino]butanoic acid
(3a). Solvent ethanol–propan-2-ol, 2:1. The filtrate
containing potassium 4-[(2-amino-2-oxoethyl)amino]-
butanoate was acidified with 2 equiv of acetic acid,
and compound 3a separated from the solution as
an acetic acid salt. Yield 62–64%. Recrystallization
from methanol gave amino acid 3a as colorless prisms,
153°C (from H2O). H NMR spectrum (D2O), δ, ppm:
2.49–2.68 m (2H, CH2), 3.36–3.45 m (2H, CH2),
3.56 quint (1H, CH, J = 8.0 Hz), 3.76–3.85 m (2H,
CH2), 7.58 t (1H, Harom, J = 8.0 Hz), 7.71 d (1H, Harom
,
J = 4.0 Hz), 8.14 d (1H, Harom, J = 4.0 Hz), 8.19 br.s
(1H, Harom). Found, %: C 51.28; H 5.32; N 14.88.
C12H15N3O5. Calculated, %: C 51.24; H 5.38; N 14.94.
1
mp 150–151°C (from MeOH). H NMR spectrum
(1-{[(2-Amino-2-oxoethyl)amino]methyl}cyclo-
hexyl)acetic acid (3g). Solvent propan-2-ol. After
addition of all reactants, the mixture was heated for 4 h
at 75°C, the resulting suspension was cooled to room
temperature, the precipitate of potassium chloride was
filtered off, and the filtrate was diluted with two
volumes of acetone, acidified with acetic acid, cooled
to –5°C, and left to stand for 24 h at that temperature.
The precipitate of initial [1-(aminomethyl)cyclohexyl]-
acetic acid was filtered off and washed with acetone,
the filtrate was concentrated to 25% of the initial
volume under reduced pressure, the residue was cooled
to –5°C and kept for 24 h, and the crystalline solid was
filtered off and washed with acetone. Yield 79–80%,
white prisms, mp 142–143°C (from acetone). 1H NMR
spectrum (D2O), δ, ppm: 1.28–1.49 m (10H, C5H10),
2.31 s (2H, CH2), 3.25 s (2H, CH2), 3.95 s (2H, CH2).
(D2O), δ, ppm: 1.87 quint (1H, CH, J = 8.0 Hz), 2.26 t
(2H, CH2, J = 8.0 Hz), 3.04 t (2H, CH2, J = 8.0 Hz),
3.84 s (2H, CH2). Found, %: C 44.87; H 7.49; N 17.39.
C6H12N2O3. Calculated, %: C 44.99; H 7.55; N 17.49.
4-[(2-Amino-2-oxoethyl)amino]-3-phenylbutanoic
acid (3b). Solvent ethanol. Yield 62–64%, colorless
prisms, mp 148–149°C (from aqueous acetone).
1H NMR spectrum (D2O), δ, ppm: 2.48–2.63 m (2H,
CH2), 3.33–3.44 m (3H, CH2, CH), 3.73–3.77 m (2H,
CH2), 7.30–7.32 m (3H, Harom), 7.36–7.40 m (2H,
H
arom). Found, %: C 60.94; H 6.76; N 11.81.
C12H16N2O3. Calculated, %: C 61.00; H 6.83; N 11.86.
4-[(2-Amino-2-oxoethyl)amino]-3-(2,4-dichloro-
phenyl)butanoic acid (3c). Solvent ethanol–propan-2-
ol, 2:1. Yield 50–51%, light brown prisms, mp 147–
150°C (decomp.; from H2O). 1H NMR spectrum (D2O),
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SYNTHESIS OF SUBSTITUTED 2-(2-OXOPYRROLIDIN-1-YL)ACETAMIDES
877
Found, %: C 57.80; H 8.72; N 12.19. C11H20N2O3.
Calculated, %: C 57.87; H 8.83; N 12.27.
(DMSO-d6), δ, ppm: 2.35–2.42 m (1H, Heq), 2.61–
2.68 m (1H, Hax), 3.37–3.41 m (1H, Heq), 3.56 quint
(1H, CH, J = 8.0 Hz), 3.69–3.74 m (1H, Hax), 3.75 s
(3H, OCH3), 3.81 s (2H, CH2), 6.85 d (2H, Harom, J =
4.0 Hz), 7.00 br.s (1H, NH2), 7.23 d (2H, Harom, J =
4.0 Hz), 7.35 br.s (1H, NH2).
Compounds 4a–4g (general procedure). A suspen-
sion of 5 g of 3a–3g in 30 mL of anisole or o-xylene
was heated with stirring until it became homogeneous
with simultaneous removal of water by distillation.
The mixture was allowed to cool down, and the
precipitate was filtered off, washed with propan-2-ol,
and dried.
2-[4-(3-Nitrophenyl)-2-oxopyrrolidin-1-yl]acet-
amide (4f). Solvent anisole. Yield 94–95%, light
1
brown prisms, mp 172–174°C (from EtOH). H NMR
spectrum (DMSO-d6), δ, ppm: 2.45–2.55 m (1H, Heq),
2.73–2.80 m (1H, Hax), 3.47–3.53 m (1H, Heq), 3.77–
3.91 m (4H, Hax, CH2, CH), 7.05 br.s (1H, NH),
7.40 br.s (1H, NH), 7.63 t (1H, Harom, J = 8.0 Hz),
7.84 d (1H, Harom, J = 4.0 Hz), 8.10 d (1H, Harom, J =
4.0 Hz), 8.24 br.s (1H, Harom). Found, %: C 54.66;
H 4.87; N 15.85. C12H13N3O4. Calculated, %: C 54.75;
H 4.98; N 15.96.
2-(2-Oxopyrrolidin-1-yl)acetamide (4a). Solvent
anisole. Yield 70–75%, white prisms, mp 152–153°C
(from i-PrOH); published data: mp 151.5–152.5 [3],
1
150–153°C [11]. H NMR spectrum (D2O), δ, ppm:
2.01 quint (2H, CH2, J = 8.0 Hz), 2.39 t (2H, CH2,
J = 8.0 Hz), 3.43 t (2H, CH2, J = 8.0 Hz), 3.92 s
(2H, CH2).
2-(2-Oxo-4-phenylpyrrolidin-1-yl)acetamide
(4b). Solvent anisole. Yield 95–97%, white prisms,
mp 130–131°C (from i-PrOH); published data:
mp 132°C [4], 129.5–130.5°C [5]. 1H NMR spectrum
(DMSO-d6), δ, ppm: 2.38–2.45 m (1H, Heq), 2.66–
2.73 m (1H, Hax), 3.40–3.44 m (1H, Heq), 3.62 quint (1H,
CH, J = 8.0 Hz), 3.73–3.78 m (1H, Hax), 3.83 s (2H,
CH2), 7.10 br.s (1H, NH2), 7.22–7.27 m (1H, Harom),
7.33 d (4H, Harom, J = 2.0 Hz), 7.42 br.s (1H, NH2).
2-(3-Oxo-2-azaspiro[4.5]decan-2-yl)acetamide
(4g). Solvent o-xylene. Yield 83%, colorless prisms,
1
mp 141.5–142.5°C (from i-PrOH). H NMR spectrum
(DMSO-d6), δ, ppm: 1.32–1.59 m (10H, C5H10), 2.12 s
(2H, CH2), 3.16 s (2H, CH2), 3.73 s (2H, CH2), 6.97
br.s and 7.31 br.s (1H each, NH2).
4-[Bis(2-amino-2-oxoethyl)amino]-3-phenylbuta-
noic acid (5b) was synthesized according to the proce-
dure described above for compounds 3 using 3b as
amino acid substrate and ethanol as solvent. The
filtrate was acidified with concentrated aqueous HCl to
pH 4, the precipitate was filtered off, and the filtrate
was evaporated to dryness. The residue was dissolved
in a minimum amount of methanol, the solution was
filtered, and the product was precipitated by slowly
adding an equal volume of propan-2-ol. The precipitate
was filtered off and dried at 75°C. Acid 5b was
characterized as sodium salt. Yield 65–70%, colorless
prisms flowing on exposure to air, mp 171–173°C.
1H NMR spectrum (D2O), δ, ppm: 2.31–2.37 m and
2.49–2.54 m (1H each, CH2), 2.76–2.90 m (2H, CH2),
3.08–3.25 m (5H, CH2, CH), 7.19–7.33 m (5H, Harom).
Found, %: C 53.26; H 5.67; N 13.24. C14H18N3NaO4.
Calculated, %: C 53.33; H 5.75; N 13.33.
2-[4-(2,4-Dichlorophenyl)-2-oxopyrrolidin-1-yl]-
acetamide (4c). Solvent o-xylene. Yield 91‒95%, light
1
brown plates, mp 156–158°C (from EtOH). H NMR
spectrum (DMSO-d6), δ, ppm: 2.34–2.40 m (1H, Heq),
2.72–2.78 m (1H, Hax), 3.43–3.47 m (1H, Heq), 3.78–
3.88 m (3H, Hax, CH2), 3.98 quint (1H, CH, J =
8.0 Hz), 7.02 br.s (1H, NH2), 7.37 d (1H, Harom, J =
4.0 Hz), 7.39 br.s (1H, NH2), 7.48 s (1H, Harom), 7.64 d
(1H, Harom, J = 4.0 Hz). Found, %: C 50.11; H 4.13;
Cl 24.59; N 9.68. C12H12Cl2N2O2. Calculated, %:
C 50.19; H 4.21; Cl 24.69; N 9.76.
2-[4-(4-Chlorophenyl)-2-oxopyrrolidin-1-yl]-
acetamide (4d). Solvent anisole. Yield 90–91%, color-
less prisms, mp 138–140°C (from i-PrOH); published
1
data [6]: mp 133–136°C. H NMR spectrum
(DMSO-d6), δ, ppm: 2.36–2.43 m (1H, Heq), 2.66–
2.72 m (1H, Hax), 3.39–3.43 m (1H, Heq), 3.63 quint
(1H, CH, J = 8.0 Hz), 3.73–3.78 m (1H, Hax), 3.78–
3.86 m (2H, CH2), 7.03 br.s (1H, NH2), 7.32–7.37 m
(5H, Harom, NH2).
[(2-Amino-2-oxoethyl)amino]acetic acid (8) was
synthesized as described above for compounds 3 using
methanol as solvent. Yield 50%, colorless prisms,
1
mp 192–194°C (decomp., from DMF). H NMR spec-
trum (D2O), δ, ppm: 3.60 s (2H, CH2), 3.88 s (2H,
CH2). 13C NMR spectrum (D2O), δC, ppm: 47.38 and
48.98 (CH2), 168.51 (CONH2), 170.92 (COOH).
Found, %: C 36.29; H 6.01; N 21.13. C4H8N2O3.
Calculated, %: C 36.36; H 6.10; N 21.20.
2-[4-(4-Methoxyphenyl)-2-oxopyrrolidin-1-yl]-
acetamide (4e). Solvent o-xylene. Yield 90–93%,
colorless prisms, mp 118–120°C (from i-PrOH);
1
published data [7]: mp 117–118°C. H NMR spectrum
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KAVINA et al.
878
6. Vachner, C., Vachner, M.-P., Flouquet, N., Debaert, M.,
3-[(2-Amino-2-oxoethyl)amino]propanoic acid
and Berthelot, P., J. Heterocycl. Chem., 1998, vol. 35,
p. 579.
7. Berestovitskaya, V.M., Vasil’eva, O.S., Ostroglya-
dov, E.S., Petrov, V.I., Tyurenkov, I.N., and Bagme-
tova, V.V., RU Patent no. 2437659, 2010; Byull.
Izobret., 2011, no. 36.
(10) was synthesized as described above for com-
pounds 3 using ethanol as solvent. Yield 70–71%,
colorless prisms, mp 189–190°C (decomp., from
DMF). 1H NMR spectrum (D2O), δ, ppm: 2.53 t (CH2,
J = 8.0 Hz), 3.21 t (2H, CH2, J = 8.0 Hz), 3.86 s (2H,
CH2). 13C NMR spectrum (D2O), δ, ppm: 32.25, 44.61,
47.50 (CH2); 168.46 (CONH2), 177.86 (COOH).
Found, %: C 40.99; H 6.81; N 19.12. C5H10N2O3. Cal-
culated, %: C 41.09; H 6.90; N 19.17.
8. Granik, V.G. and Grizik, S.I., RU Patent no. 2032668,
1992; Byull. Izobret., 1995, no. 24.
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Ziemelis, K.M., USSR Inventor’s Certificate
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Besova, E.A., and Baukov, Yu.I., Russ. J. Gen. Chem.,
1997, vol. 67, no. 11, p. 1736.
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