Methyl nitroacetate and 3-nitropropionate in the synthesis of hexahydropyrimidines and piperidines

Article abstract of DOI:10.1007/s10593-008-0011-y

Treatment of methyl nitroacetate and 3-nitropropionate with formaldehyde and primary amines under Mannich reaction conditions gives 5- nitrohexahydropyrimidines. In the case of methyl nitroacetate both the 5-nitrohexahydropyrimidine and isomeric 3,5-di(me

Full text of DOI:10.1007/s10593-008-0011-y

Chemistry of Heterocyclic Compounds, Vol. 44, No. 1, 2008
METHYL NITROACETATE
AND 3-NITROPROPIONATE
IN THE SYNTHESIS OF HEXA-
HYDROPYRIMIDINES
AND PIPERIDINES
R. R. Shakirov1, T. V. Dokichev2, R. Z. Biglova2, N. M. Vlasova1,
N. Z. Baibulatova1, and R. F. Talipov2
Treatment of methyl nitroacetate and 3-nitropropionate with formaldehyde and primary amines under
Mannich reaction conditions gives 5-nitrohexahydropyrimidines. In the case of methyl nitroacetate both
the 5-nitrohexahydropyrimidine and isomeric 3,5-di(methoxycarbonyl)-1-methyl-3,5-dinitropiperidines
are formed.
Keywords: hexahydropyrimidines, 3,5-dinitropiperidines, methyl nitrocarboxylates, Mannich reaction.
The reaction of primary amines and formaldehyde with compounds containing a mobile hydrogen atom
on a carbon atom is widely used in organic synthesis as a convenient method for preparing tetrahydro-
1,3-oxazines, hexahydropyrimidines [1, 2], and also 3-aza- [3-6] and 3,7-diazabicyclo[3,3,1]nonanes [3, 7-15].
Members of this class of compounds show high physiological activity and are used in medical practice as
antimicrobial, antiviral, antitumor and other medicinal agents [10-12, 16]. It is known that nitro–substituted
heterocyclic compounds show increased antibacterial activity [1], can behave as sources of nitric oxide [17] in
the human organism, and they are of interest both as chemotherapeutic agents and as intermediates in organic
synthesis. Hence 5-[2-(methoxycarbonyl)ethyl]-1,3-dimethyl-5-nitrohexahydropyrimidine shows clear anti-
arrythmic activity [18] and trinitrohexahydropyrimidine (containing a glutaric acid fragment) is a convenient
synthon for preparing immunologically active peptide conjugates [19] used in immunoenzymic analysis.
Condensation with a nitro compound has shown promise in the synthesis of novel, practically important
polyfunctional six–membered nitrogen heterocycles. According to literature data the course of the reaction of
aliphatic mononitroalkanes with formaldehyde and primary amines depends on the structure of the starting
reagents, their ratio, the temperature, and the nature of the solvent and it can occur to form amines,
diaminopropanes, tetrahydrooxazines, and hexahydropyrimidines [1, 2]. It has been shown previously that the
reaction of methyl 4-nitrobutanoate with methylamine hydrochloride and CH2O occurs in 40% yield to give
5-nitro-5-[2-(methoxycarbonyl)ethyl]-1,3-dimethyl-hexahydropyrimidine and it is formed exclusively via the
CH2NO2 fragment of the starting nitrobutanoate [18].
__________________________________________________________________________________________
1Institute of Organic Chemistry, Ufa Science Center of the Russian Academy of Sciences, Ufa 450054,
Russia; e-mail: dokichev@anrb.ru. 2Bashkir State University, Ufa 450074, Russia; e-mail:
interdpt@bsu.bashedu.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 53-60, January,
2008. Original article submitted March 9, 2007.
0009-3122/08/4401-0043©2008 Springer Science+Business Media, Inc.
43

In this work we report the synthesis of a series of nitro-substituted hexahydropyrimidines and
piperidines via the condensation of methyl nitroacetate or 3-nitropropionate with formaldehyde and primary
amines under Mannich reaction conditions and a study of the effect of the structure of the starting components
and reaction conditions on the yield and composition of the products formed. It should be stressed that this work
is of interest in a scheme of developing novel routes to amino acids of synthetic origin.
Methyl nitroacetate (1) and 3-nitropropionate (2) were used as the nitrocarboxylic esters and methyl- (3),
isopropyl- (4), and benzylamine (5) as the primary amines. Experiments were carried out by refluxing in
methanol for 4 h with a 1:10:5 molar ratio of the methyl nitrocarboxylate, formaldehyde, and amine. In these
chosen conditions it was found the methyl nitroacetate 1 reacts with formaldehyde (as a 35% formalin solution)
and 25% methylamine to give a 98% yield of 5-(methoxycarbonyl)-1,3-dimethyl-5-nitrohexahydropyrimidine
(6) with high selectivity. It should be noted that 5-nitrohexahydropyridines were prepared in the study [20] in
two stages from ethyl nitroacetate.
The route of condensation of methyl nitroacetate 1 depends markedly on the nature of the solvent
(Scheme 1). Hence use of chloroform lowers the reaction selectivity and gives the hexahydropyrimidine (6)
together with the 3,5-dimethoxycarbonyl-1-methyl-3,5-dinitropiperidines (7) in overall yield 80% and in the
1
13
ratio 3:1. According to H and C NMR data the piperidine 7 exists as a 1:1 mixture of the two diastereomers
7a,b differing in the cis and trans positioning of the NO2 groups.
Scheme 1
O2N
CO2Me
MeOH
O2NCH2CO2Me
4 h, 65°C, 98%
N
N
1
Me
Me
+
6
CH2O
CO2Me
MeO2C
MeO2C
O2N
NO2
CO2Me
+
MeNH2
3
CHCl3
6
+
O2N
NO2 +
20°C, 80%
N
N
Me
Me
7a
7b
6 : 7a : 7b = 6 : 1 : 1
The reaction of methyl nitroacetate 1 with isopropylamine 4 and formaldehyde in methanol (Scheme 2)
gives the expected hexahydropyrimidine 8 along with the 5-hydroxymethyl-5-nitrohexahydropyrimidine (9) in
35 and 17% yield respectively. The nitro alcohol 9 is likely formed as a result of hydrolysis
Scheme 2
NO2
CH2O
N
N
i-Pr
O2N
i-Pr
O2NCH2CO2Me
10
1
O2N
N
CO2Me
OH
+
CH2O
MeOH
+
4 ч, 65 oC
N
N
N
i-Pr
i-Pr
i-Pr
i-Pr
+
i-PrNH2
4
9, 17%
8, 35%
44

and decarboxylation of compound 8 and subsequent reaction of the 1,3-diisopropyl-5-nitrohexahydropyrimidine
(10) formed with a molecule of formaldehyde via a Henry reaction [21, 22]. The structure of the
1
13
hexahydropyrimidine 9 was identified from H and C NMR spectroscopic data. The methylene protons in the
1
CH2OH group appear in the H NMR spectrum as a singlet at 4.0 ppm and the presence of this hydroxymethyl
group is also confirmed by the carbon atom signal for the CH2OH fragment at 66.0 ppm in the 13C NMR
spectrum.
A study of the effect of the nature of the starting reagents on the reaction route showed a marked
dependence on the amine component. Hence, by contrast with methylamine and isopropylamine, the
condensation of the methyl nitroacetate 1 with benzylamine 5 and CH2O occurs nonselectively upon refluxing in
methanol (Scheme 3) to give an overall yield of 70% of a mixture of 1,3-dibenzyl-5-methoxycarbonyl-
5-nitrohexahydropyrimidine (11), and cis- 12a and trans-3,5-bis(methoxycarbonyl)-3,5-dinitropiperidine (12b)
in the ratio 6:1:1 which were separated using column chromatography. The ratio of the isomers 12a and 12b was
1
determined from the H NMR spectrum of the reaction mixture based on the integrated intensities of the OMe
group proton signals, the chemical shifts of which are 3.79 and 3.81 ppm.
Scheme 3
BnNH
O NCH CO Me
CH O
+
+
2
2
2
2
2
1
5
MeOH
4 h, 65°C, 70%
NO2
CO2Me
MeO2C
O2N
CO2Me
O2N
N
CO2Me
MeO2C
O2N
NO2
+
+
N
N
N
Bn
Bn
Bn
Bn
11
12a
12b
11 : 12a : 12b = 6 : 1 : 1
In the case of the methyl 3-nitropropionate 2 the formation of a piperidine fragment was not observed
under the Mannich reaction conditions. The reaction of the methyl 3-nitropropionate 2 with methylamine and
formaldehyde in methanol at 65ºC over 4 h gave the 5-methoxycarbonylmethyl-1,3-dimethyl-5-nitrohexa-
hydropyrimidine (13) and 5-methoxycarbonylmethylidene-1,3-dimethyl-hexahydropyrimidine (14) in 47 and
51% yields respectively. Lowering the temperature to 20ºC led to an increase in the yield of heterocycle 13 to
70% (Scheme 4).
Scheme 4
Bu2NH
4 h, 20°C, 98%
CO2Me
O2N(CH2)2CO2Me
O2N
2
CO2Me
+
Me
+
MeOH
N
N
N
N
CH2O
Me
Me
Me
13
14
+
MeNH2
20°C
65°C
70%
47%
29%
51%
3
45

Formation of the unsaturated compound 14 is in agreement with literature data [23] and occurs at pH 7-8
under the action of methylamine as a result of separation of nitrous acid from the hexahydropyrimidine molecule
13 which contains an active methylene group in an α-position to the CO2Me group. It was found experimentally
that stirring the hexahydropyrimidine 13 in dibutylamine taken as the base gives a quantitative yield of the
heterocycle 14.
The structure of the synthesized compounds separated by column chromatography was confirmed from
1
their H and 13C NMR spectroscopic data using the homo- and heteronuclear HH COSY and CH CORR
13
methods. The C NMR spectra of the hexahydropyrimidines 6, 8, 9, 11, 13, 14 show characteristic signals for
the NCH2N group carbon atoms in the range 70.3-78.5 ppm. The signal at 77.4 ppm in the carbon spectrum of
the 5-methoxycarbonyl-1,3-dimethyl-5-nitrohexahydropyrimidine 6 for the NCH2N fragment correspond to the
axial and equatorial protons seen at 2.72 and 3.35 ppm respectively in the proton spectrum.
Hence a one-pot method has been developed for the synthesis of hexahydropyrimidines and
3,5-dinitropiperidines via reaction of methyl nitrocarboxylates with formaldehyde and primary amines. It was
found that the reaction route depends of the structure of the starting reagents and the conditions used.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Bruker AM-300 spectrometer (300 and 75 MHz
respectively) using CDCl3 and with TMS as internal standard. IR spectra were obtained on a Specord M-80
instrument as a thin film and mass spectra on an MX-1300 spectrometer with an inlet system heated at 100ºC
and ionizing intensities of 12 and 70 eV. GLC Analysis was performed on a Chrom-5 chromatograph with flame
ionization detection (column 1200×5 mm, 5% SE-30 on Inerton N-AW DMCS (0.125-0.160 mm, and helium
gas carrier). Elemental analysis was performed on an HEKAtech Gmbh Analysen-technik's Euro-EA CHN
analyzer. TLC was performed on Merck Silufol plates. Preparative separations were carried out using column
chromatography on SiO2 from the Lancaster company (70-230 mesh).
Methyl 2-nitroacetate (1) and 3-nitropropionate (2) were synthesized by known methods [24, 25].
Reaction of Methyl Nitroacetate and 3-Nitropropionate with Formaldehyde and Primary Amines
(General Method). Formalin (2.93 ml, 35%, 37.6 mmol of CH2O) and the primary amine (18.8 mmol) were
added to a solution of the methyl nitrocarboxylate (3.76 mmol) in MeOH (27 ml) which was stirred with a
magnetic stirrer and the product was refluxed with a reflux condenser for 4 h. Methanol was distilled off under
reduced pressure and chloroform (18 ml) was added. The reaction mixture was washed with water (3×10 ml),
dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The residue was
chromatographed on a silica gel column (eluent CHCl3–2-PrOH, 9:1).
5-Methoxycarbonyl-1,3-dimethyl-5-nitrohexahydropyrimidine (6) was obtained at 65ºC from methyl
nitroacetate 1, (10 g, 8.4 mmol), aqueous formalin (35%, 6.99 ml, 84 mmol), and aqueous methylamine (25.2%,
5.17 g, 42 mmol) as an oil (1.81 g, 98%). IR spectrum, ν, cm-1: 1384, 1552 (NO2), 1284, 1712 (CO2). 1H NMR
spectrum, δ, ppm (J, Hz): 2.28 (6H, s, 2CH3); 2.72 (1Hax, d, 2J = 9.2, NCH2N); 2.77 (2Hax, d, 2J = 12.6, 2CH2N);
2
2
13
3.35 (1Heq, d, J = 9.2, NCH2N); 3.56 (2Heq, d, J = 12.6, 2CH2N); 3.77 (3H, s, OCH3). C NMR spectrum, δ,
ppm: 42.2 (NCH3); 53.79 (OCH3); 56.8 (CH2N); 77.4 (NCH2N); 89.0 (CNO2); 164.9 (CO2). Mass spectrum, m/z:
217 [M]+. Found, %: C 44.35; H 7.00; N 19.20. C8H15N3O4. Calculated, %: C 44.23; H 6.96; N 19.34.
When carrying out the reaction in chloroform (20ºC, 4 h) the yield of the hexahydropyrimidine 6 was
48% together with the piperidines 7a and 7b in 32% overall yield.
cis-3,5-Bis(methoxycarbonyl)-1-methyl- (7a) and trans-3,5-Bis(methoxycarbonyl)-1-methyl-
3,5-dinitropiperidines (7b). IR spectrum, ν, cm-1: 1540 (NO2), 1738 (C=O). Mass spectrum, m/z: 305 [M]+.
Found, %: C 39.10; H 4.95; N 13.77. C10H15N3O8. Calculated, %: C 39.35; H 4.95; N 13.77.
46

cis-3,5-Di(methoxycarbonyl)-1-methyl-3,5-dinitropiperidine (7a). 1H NMR spectrum, δ, ppm (J, Hz):
2
2
2
2.42 (3H, s, NCH3); 2.78 (2Hax, d, J = 13.2, 2CH2N); 3.18 (1Hax, d, J = 16.2, CH2); 3.52 (2Heq, d, J = 13.2,
2
13
2CH2N); 3.63 (1Heq, d, J = 16.2, CH2); 3.84 (6H, s, 2OCH3). C NMR spectrum, δ, ppm: 33.4 (CH2); 45.2
(NCH3); 54.3 (OCH3); 58.1 (CH2N); 88.9 (CNO2); 165.3 (CO2).
1
trans-3,5-Di(methoxycarbonyl)-1-methyl-3,5-dinitropiperidine (7b). H NMR spectrum, δ, ppm (J,
2
2
Hz): 2.44 (3H, s, NCH3); 3.08 (2Hax, d, J = 12.3, 2CH2N); 3.21 (2Heq, d, J = 12.3, 2CH2N); 3.32 (2H, br. s,
13
CH2); 3.86 (6H, s, 2OCH3). C NMR spectrum, δ, ppm: 33.5 (CH2); 45.2 (NCH3); 54.2 (OCH3); 58.5 (CH2N);
89.3 (CNO2); 164.9 (CO2).
1,3-Diisopropyl-5-methoxycarbonyl-5-nitrohexahydropyrimidine (8) and 5-Hydroxymethyl-
1,3-diisopropyl-5-nitrohexahydropyrimidine (9). From methyl nitroacetate 1 (1.0 g, 8.4 mmol), aqueous
formalin (35%, 6.55 ml, 84 mmol), and diisopropylamine (3.63 ml, 42 mmol) to give compound 8 (0.81 g,
35.3%) and compound 9 (0.36 g, 17.5%) as a yellow-colored oil.
1,3-Diisopropyl-5-methoxycarbonyl-5-nitrohexahydropyrimidine (8). IR spectrum, ν, cm-1: 1368,
1
1384 (gem-dimethyl group doublet); 1368, 1552 (NO2); 1176, 1752 (CO2). H NMR spectrum, δ, ppm (J, Hz):
3
2
2
1.02 and 1.07 (12H, two d, J = 6.6, 4CH3); 2.87 (2H, sept, J = 6.6, 2CH); 2.93 (2Hax, d, J = 12.0, 2CH2N);
3.16 (1Hax, d, 2J = 8.7, NCH2N); 3.53 (1Heq, d, 2J = 8.7, NCH2N); 3.62 (2Heq, d, 2J = 12.0, 2CH2N); 3.78 (3H, s,
13
OCH3). C NMR spectrum, δ, ppm: 17.54 and 18.91 (both CH3); 50.68 (CH2N); 52.38 (OCH3); 53.50 (CHN);
70.30 (NCH2N); 89.60 (CNO2); 165.36 (CO2). Mass spectrum, m/z: 273 [M]+. Found, %: C 52.69; H 8.48;
N 15.37. C12H23N3O4. Calculated, %: C 52.73; H 8.48; N 15.37.
5-Hydroxymethyl-1,3-diisopropyl-5-nitrohexahydropyrimidine (9). IR spectrum, ν, cm-1: 1168 (gem
dimethyl group doublet); 1364, 1568 (NO2); 3264 (OH). 1H NMR spectrum, δ, ppm (J, Hz): 1.05 and 1.09 (12H,
two d, 3J = 6.6, 4CH3); 2.79 (2Hax, d, 2J = 12.0, 2CH2N); 2.88 (2H, sept, 2J = 6.6, 2CH); 3.27 (2Heq, d, 2J = 12.0,
2
2
2CH2N); 3.32 (1Hax, d, J = 8.7, NCH2N); 3.39 (1Heq, d, J = 8.7, NCH2N); 4.00 (2H, s, CH2OH); 4.12 (1H, s,
13
OH). C NMR spectrum, δ, ppm: 17.73 and 18.87 (both CH3); 50.37 (CH2N); 52.55 (CHN); 66.00 (CH2OH);
70.62 (NCH2N); 88.65 (CNO2). Mass spectrum, m/z: 245 [M]+. Found, %: C 53.84; H 9.46; N 17.15.
C11H23N3O3. Calculated, %: C 53.86; H 9.45; N 17.13.
1,3-Dibenzyl-5-methoxycarbonyl-5-nitrohexahydropyrimidine (11), 1-Benzyl-cis-3,5-bis(methoxy-
carbonyl)- (12a) and 1-Benzyl-trans-3,5-bis(methoxycarbonyl)-3,5-dinitropiperidine (12b). From methyl
nitroacetate 1 (1.0 g, 8.4 mmol), aqueous formalin (35%, 6.55 ml, 84 mmol), and benzylamine (4.6 ml, 42
mmol) to give compound 11 (1.02 g, 33%) and compounds 12a,b (0.04 g, 2.5%) as a yellow-colored oil.
1,3-Dibenzyl-5-methoxycarbonyl-5-nitrohexahydropyrimidine (11). IR spectrum, ν, cm-1: 1360,
1
1552 (NO2); 1264, 1748 (CO2); 704, 752, 1456, 3032, 3048, 3064 (C6H5). H NMR spectrum, δ, ppm (J, Hz):
2
2
2
3.04 (2Hax, d, J = 12.8, 2CH2N); 3.07 (1Hax, d, J = 9.9, NCH2N); 3.53 (1Heq, d, J = 9.9, NCH2N); 3.59 and
3.67 (4H, two d, 2J = 13.4, 2PhCH2N); 3.75 (3H, s, OCH3); 3.78 (2Heq, d, 2J = 12.8, CH2N); 7.18-7.45 (10H, m,
2Ar). 13C NMR spectrum, δ, ppm: 53.57 (OCH3); 55.50 and 58.40 (CH2N); 72.58 (NCH2N); 89.00 (CNO2);
127.24 (p-CPh); 128.18 and 128.68 (o- and m-CPh); 137.03 (i-CPh); 165.15 (CO2). Mass spectrum, m/z: 369 [M]+.
Found, %: C 65.05; H 6.25; N 11.38. C20H23N3O4. Calculated, %: C 65.03; H 6.28; N 11.37.
1-Benzyl-cis-3,5-bis(methoxycarbonyl)- (12a) and 1-Benzyl-trans-3,5-bis(methoxycarbonyl)-
3,5-dinitropiperidine (12b). IR spectrum, ν, cm-1: 1340, 1550 (NO2); 1250, 1760 (CO2); 710, 750, 1450, 1490
(C6H5). 1H NMR spectrum, δ, ppm (J, Hz) 12a: 2.91 (2Hax, d, 2J = 12.7, CH2N); 3.19 (1HAB, d, 2J = 15.9, CH2);
2
2
3.55 (2Heq, d, J = 12.7, 2CH2N); 3.61 (1HAB, d, J = 15.9, CH2); 3.68-3.76 (2H, m, C6H5CH2N); 3.79 (6H, s,
2OCH3); 7.16-7.45 (5H, m, Ar). 1H NMR spectrum, δ, ppm (J, Hz) 12b: 3.19 (1HAB, d, 2J = 15.5, 2CH2N); 3.29
(2HAB, d, 2J = 12.5 CH2N); 3.35 (2H, br. s, CH2); 3.68-3.76 (2H, m, C6H5CH2N); 3.81 (6H, s, 2OCH3); 7.16-7.45
13
(5H, m, Ar). C NMR spectrum, δ, ppm, 12a: 54.10 (OCH3); 56.00 (CH2N); 58.55 (CPhCH2N); 88.80 (CNO2);
13
165.10 (CO2). C NMR spectrum, δ, ppm, 12b: 34.10 (CH2); 54.00 (OCH3); 56.29 (CH2N); 58.73 (CPhCH2N);
89.22 (CNO2); 127.95; 128.42; 129.09, 129.20, 129.33 and 135.45 (CPh); 164.88 (CO2). Mass spectrum, m/z: 381
[M]+. Found, %: C 50.41; H 5.05; N 10.99. C16H19N3O8. Calculated, %: C 50.39; H 5.02; N 11.02.
47

5-Methoxycarbonylmethyl-1,3-dimethyl-5-nitrohexahydropyrimidine (13) and 5-methoxy-
carbonylmethylidene-1,3-dimethylhexahydropyrimidine (14). From methyl 3-nitropropionate 2, (0.5 g, 3.76
mmol), aqueous formalin (35%, 2.93 ml, 37.6 mmol), and aqueous methylamine (25.2%, 2.31 g, 18.8 mmol) to
give compound 13 (0.42 g, ~ 47%) and compound 14 (0.36 g, ~ 51%). Lowering the reaction temperature to
20ºC leads to an increase in the yield of the hexahydropyrimidine 13 to 70% and the yield lowering of
compound 14 to 29%.
5-Methoxycarbonylmethyl-1,3-dimethyl-5-nitrohexahydropyrimidine (13). IR spectrum, ν, cm-1:
1
1160, 1740 (CO2); 1370, 1550 (NO2); 2780 (CH3N). H NMR spectrum, δ, ppm (J, Hz): 2.24 (6H, s, 2CH3N);
2.79 (1Hax, d, 2J = 8.6, NCH2N); 2.87-2.94 (5H, 1Heq, m, NCH2N, 4H, 2CH2N); 3.14 (2H, s, CH2CO2); 3.63 (3H,
s, OCH3). 13C NMR spectrum, δ, ppm: 14.2 (CH3); 35.0 (CH); 33.7 (CH2CO2); 46.4 (NCH3); 51.9 (OCH3); 59.5
(CH2N); 78.5 (NCH2N); 84.4 (CNO2), 169.2 (CO2). Mass spectrum, m/z: 231 [M]+. Found, %: C 46.52; H 7.41;
N 18.17. C9H17N3O4. Calculated, %: C 46.74; H 7.41; N 18.17.
5-Methoxycarbonylmethylidene-1,3-dimethylhexahydropyrimidine (14). IR spectrum, ν, cm-1: 840
1
(C=CH); 1160, 1720 (CO2); 2770 (CH3CN). H NMR spectrum, δ, ppm (J, Hz): 2.25 and 2.29 (6H, two s,
2CH3N); 3.03 and 3.27 (4H, two s, 2CH2CN); 3.65 (3H, s, OCH3); 3.7 (2H, s, NCH2N); 5.71 (1H, s, C=CH). 13C
NMR spectrum, δ, ppm: 41.8 and 41.9 (NCH3); 51.0 (OCH3); 53.46 and 60.9 (CH2N); 77.0 (NCH2N); 115.9
(C=CH); 151.4 (C=CH); 166.2 (CO2). Mass spectrum, m/z: 184 [M]+. Found, %: C 58.72; H 8.69; N 15.17.
C9H16N2O2. Calculated, %: C 58.67; H 8.75; N 15.21.
5-Methoxycarbonylmethylidene-1,3-dimethylhexahydropyrimidine (14). A solution of 13 (0.5 g,
2.20 mmol) in Bu2NH (5 ml, 29.68 mmol) was stirred for 4 h at 20ºC, dissolved in chloroform (10 ml), washed
with water (3 x 10 ml), and dried over Na2SO4. The solvent was removed under reduced pressure to give
compound 14 (0.39 g, 98%) as an oil.
This work was carried out with the financial support of the Basic Research Program of the Presidium of
the Russian Academy of Sciences "Study of methods for preparing chemical materials and development of novel
materials"
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