Claisen condensation of N-methylpyrrolidinone and α-chloronicotinic esters

Article abstract of DOI:10.1002/jhet.5570450128

Reaction between α-halo-nicotinic esters and a nucleophilic source such as the N-methylpyrrolidin-2-one (NMP) gave unexpected results. The presence of the halide on the pyridine gave a very interesting migration reaction. Extension to 6-methylnicotinic ester derivatives lead to an unexpected carbanion condensation.

Full text of DOI:10.1002/jhet.5570450128

Jan-Feb 2008
229
Claisen Condensation of N-Methylpyrrolidinone
and ꢀ-Chloronicotinic esters
Thomas Kaminski, Gilbert Kirsch*
Laboratoire d’Ingénierie Moléculaire et Biochimie Pharmacologique
Institut Jean Barriol, Université Paul Verlaine-Metz, 1, Boulevard Arago, 57078, Metz, France.
Email: kirsch@univ-metz.fr
Received June 6, 2007
O
O
O
NaH, NMP,
THF, reflux
OR
N
Cl
N
RO
N
Reaction between ꢀ-halo-nicotinic esters and a nucleophilic source such as the N-methylpyrrolidin-2-
one (NMP) gave unexpected results. The presence of the halide on the pyridine gave a very interesting
migration reaction. Extension to 6-methylnicotinic ester derivatives lead to an unexpected carbanion
condensation.
J. Heterocyclic Chem., 45, 229 (2008).
INTRODUCTION
by varying the pyrrolidinone N-alkyl side chain [3]
(Scheme III).
N-Alkyl-3-nicotinoyl-pyrrolidin-2-ones are very inter-
esting intermediates for the synthesis of 4-(N-methyl-
nitrosamine)-1-(3pyridinyl)-1-butanone derivatives (NNK,
Scheme I). NNK is a nitrosamine present in tobacco
smoke, which is a procarcinogen. It is activated by
CYP2A6 [1a] and acts as a biomarker of exposure to
cigarette smoke and smoking addiction.
Scheme III
O
R
O
O
O
N
X
X
OEt NaH
R
N
THF, reflux
N
N
X = H, F, Cl, Br, I
R = Me, Et,
Scheme I
O
O
N
N
In order to extend this type of precursors for
immunological tests, our objective was the synthesis of 3-
[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolidin-
one derivatives (8), by applying the same method to 6-
chloronicotinates (4b) (Scheme IV).
N
NNK
Synthesis of these NNK derivatives has been described
starting from ethylnicotinate, which reacts with NMP to
give N-methyl-3-nicotinoyl-pyrrolidin-2-one. The resul-
ting lactam was opened under strong acidic conditions.
Nitrosation of the secondary amine afforded NNK in good
yield [1] (Scheme II).
Scheme IV
O
R
N
O
O
O
OEt NaH
R
N
THF, reflux
Cl
N
Cl
N
4b
8
Scheme II
O
O
O
NaH, NMP
THF, reflux
RESULTS AND DISCUSSION
OEt
N
First we synthesized the 6-hydroxynicotinic acid (2) by
a modification of the method described by Von Pechmann
[4,5,6]. Coumalic acid (1) previously prepared by using
fuming sulfuric acid, was synthesized in concentrated
sulfuric acid (2 mL/g of malic acid). The reaction was
slower, but yield was similar and the acidic waste was
lowered in this manner. 6-Hydroxynicotinic acid (3) was
obtained from methyl coumalate (2) and transformed to 6-
N
N
O
O
N
N
1) HCl, reflux,
3 days
2) NaNO2
N
Related literature describes the synthesis of NNK
derivatives starting from different nicotinic esters [2] or

230
T. Kaminski, G. Kirsch
Vol 45
Scheme VII
chloronicotinate esters (4a, 4b) using phosphorus
oxychloride and either methyl or ethyl alcohol [7] with
satisfactory yield (Scheme V).
O
O
O
N
O
N
OR
Scheme V
Cl
N
Cl
N
COOMe
1) H2SO4
2) MeOH
COOH
OH
RO
HOOC
O
O
2, 64 %
O
O
COOH
1) NH4OH
COOR
1) POCl3 reflux
2) ROH
N
2) NaOH 4M,
reflux
HO
N
Cl
N
RO
N
3, 92 %
4a, R = Me (80%)
4b, R = Et (75%)
Claisen condensation between the ester and the
carbanion formed by reaction of NMP with sodium
hydride released an ethoxy group, which made a
nucleophilic substitution of the ꢀ-chlorine on the pyridine
ring. This type of reaction has been well described in
literature [8].
To extend the study, we applied the same conditions to
different esters available from commercial 2-chloro-
nicotinic acid [9] (Table 1). These esters were reacted in
the Claisen condensation (Scheme VIII), and afforded
generally the condensation-substitution product along
with the starting material. Substitution varied with chain
length and alcohol type. In this way, tertiary alcohol did
not give the substitution product certainly due to steric
hindrance (Table 1, entry 7).
We applied the method described for the synthesis of
the 1-methyl-3-nicotinoyl-pyrrolidinone to the synthesis
of the 3-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-2-
pyrrolidinone, starting from the previously prepared ethyl
6-chloronicotinate (4b).
By monitoring the reaction by TLC, formation of a
product different from the starting material was observed.
The presence of a 1,3-diketone was confirmed when dark
blue spot appears by developing TLC plate with ethanolic
FeCl3 solution. After work up of the reaction and analysis
of the product by mass spectrometry, we noticed that the
chlorine atom was missing. Presence of a sp3 CH was
1
confirmed by H NMR experiment. In fact, signals of the
lactam were very complex to explain due to the
asymmetric carbon, making the two CH2 of the NMP
diastereotopic. Moreover new ethoxy group signals were
detected at 4.43 ppm (CH2) and 1.39 ppm (CH3), different
from the ethoxy group from the starting material (4.3 ppm
(CH2) and 1.24 ppm (CH3)). The 13C NMR experiment
shows that the carbon was linked to chlorine at 155.6 ppm
has disappeared but is still quaternary. These results lead
us to the following conclusion: the chlorine atom has been
substituted by the ethoxy group from the starting ester
(Scheme VI).
Scheme VIII
O
O
O
O
NaH (2 eq.),
NMP (2 eq.)
OR
1) SOCl2,
reflux
OH
N
2) ROH or
RONa/THF
THF, reflux
N
Cl
N
Cl
N
O
R
5
7
Table 1
O
O
O
N
OR
Entry
ROH
N
O
R
N
Cl
Scheme VI
(Yield %)
(Yield %)
1
2
3
4
5
6
7
8
CH3OH
CH3CH2OH
5a (87a)
5b (80a)
5c (51a)
5d (55a)
5e (81b)
5f (68a)
5g (59b)
5h (70b)
7a (47)
7b (46)
7c (61)
7d (55)
7e (43)
7f (54)
7g (-)
O
O
O
NaH (2 eq.),
NMP (2 eq.),
OR
CH3CH2CH2OH
(CH3)2CHOH
CH3CH2CH2CH2OH
CH3CH(OH)CH2CH3
(CH3)3COH
N
Cl
N
THF, reflux
RO
N
4a, 4b
6a, R = Me (51%)
6b, R = Et (50%)
(CH3)2CHCH2CH2OH
7h (48)
To explain this reaction, we propose the following
mechanism (Scheme VII).
Esters were prepared according to Method A (a) or B (b) described in
experimental part

Jan-Feb 2008
Claisen condensation of N-methylpyrrolidinone and ꢀ-chloronicotinic esters
231
Scheme XI
By studying this reaction, we have shown that
migration of an alkoxy group formed in situ was possible.
Steric hindrance was the only limitation of the method.
The same reaction was performed starting from ethyl 6-
methylnicotinate [10]. In fact, from the condensation we
could isolate a second compound in 45 % yield along with
the desired compound. This structure was identified as
shown in Scheme IX. In fact, the product was formed
through deprotonation of the methyl group and
condensation on the ester of a second molecule (Scheme
X). This was unexpected as normally deprotonation of
methyl pyridine occurs with stronger bases such as phenyl
lithium [11], LDA [12] or different sodium or potassium
bases [13].
O
O
O
O
N
N
N
N
N
H
HO
O
N
(E)
(Z)
Stereochemistry (Z or E) could be determined by
analogy with the study on (Z)-2-(2-hydroxy-2-phenyl-
vinyl)pyridine [14]. According to the literature, the
tautomer ratio due to hydrogen bonding depends on
solvent [15], temperature [16] and substitutions [16,17].
NMR analysis in our case shows only an enol form, which
has been assigned to the Z-isomer (Scheme XI).
Scheme IX
O
O
In summary, we have shown that
a
Claisen
O
O
O
condensation on 2 or 6-chloronicotinates or methyl-
nicotinates must be run carefully in order to avoid
unexpected side reactions.
N
NaH (2 eq.),
OEt
NMP (2eq.)
N
N
+
N
N
THF, reflux
HO
N
EXPERIMENTAL
9, 45 %
Purification by column chromatography was performed by
using silica gel 60A (0.07-0.200mm). Melting points were
To explain the reaction we propose the following
mechanism (Scheme X), involving reactivity similar to
scheme VII.
determined on
a Stuart Scientific SMP3 Melting Point
Apparatus and are uncorrected. H and 13C NMR spectra were
recorded on a AC Bruker 250 MHz spectrometer in CDCl3 or
DMSO-d6 as solvent. Elemental Analyses were done in a LECO
CHNS 932 equipment. Mass spectra were performed on a
MS/GC using Varian GC 3800 fitted with a Saturn 2000 MS and
a Maldi-ToF MS Bruker Reflex.
1
Scheme X
O
O
O
N
Coumalic acid (1). In a 2 L flask, 200 g (1.19 mol) of
malic acid were slowly added portionwise to 400 mL of
concentrated sulfuric acid (Caution: gloves and safety
glasses have to be worn). The solution was heated on a
water bath until the evolution of gas stopped. The reaction
mixture was then cooled and poured slowly onto 800 g of
crushed ice. After standing 24 hours, the acid was filtered
on a Büchner funnel, washed with three 50 mL portions of
ice cold water and dried, yielding 67% of a pale yellow
N
O
N
O
Base
OEt
N
EtO
N
1
solid. Mp= 203-205°C, Mplit= 205-208 [18]. H NMR
O
O
(250 MHz, DMSO d6): ꢁ 8.60 (s, 1H), 7.81 (d, J = 12 Hz,
1H), 6.62 (t, J = 12 Hz, 1H). 13C NMR (250 MHz, DMSO
d6): ꢁ 166.3, 160.2, 159.1, 142.8, 114.9, 112.2.
N
N
6-Hydroxynicotinic acid (3). From the above
described coumalic acid (1), access to 6-hydroxynicotinic
acid was achieved by the described procedure (using
methyl coumalate (2) as intermediate) [4,5,6].
HO
N
Preparation of alkyl 6-chloronicotinates was
described in the literature. Methyl 6-chloronicotinate
(4a) [7b, 21], ethyl 6-chloronicotinate (4b) [7].
Preparation of 2-chloronicotinoyl chloride hydro-
chloride. 0.3 Mol of SOCl2 was added carefully to 0.1
mol of 2-chloronicotinic acid; the mixture was stirred and
The NMP carbanion reacts with the nicotinic ester,
releasing an ethoxy group into the media. The acidity
of the methyl group, enhanced by the diketone in the
para position, was then deprotonated to react with
another ester, to give the ketone detected as its enol
form (Scheme X).

232
T. Kaminski, G. Kirsch
Vol 45
Isopentyl 2-chloronicotinate (5h). This compound was
obtained as a yellow oil (70%).1H NMR (250 MHz, CDCl3): ꢀ
8.42 (d, J = 12 Hz, 1H), 8.08 (d, J = 12 Hz, 1H), 7.28 (t, J = 12
Hz, 1H), 4.30 (t, 2H), 1.67 (m, 1H), 1.56 (m, 2H), 0.97 (d, 6H).
13C NMR (250 MHz, CDCl3): ꢀ 164.5, 151.6, 149.7, 140.2,
127.1, 122.1, 64.6, 37.1, 24.9, 22.3. MS (EI): m/z (%) = 158
(100), 228 (17,0, [M+H]). Anal. Calcd. for C11H14ClN2O: C,
58.03; H, 6.20; N, 6.15. Found: C, 58.19; H, 6.17; N, 6.07.
refluxed overnight. Excess of SOCl2 was removed under
vacuum to dryness. The crude product was directly used
in the following steps.
Procedure for the preparation of 2-chloronicotinic esters (4).
Method A. 0.05 mol of 2-chloronicotinoyl chloride
hydrochloride was mixed with an excess of the
appropriate alcohol and refluxed overnight. Excess of
alcohol was removed under vacuum to dryness. The
remaining product was then poured carefully onto ice
water and basified with solid NaHCO3 until the pH was
alkaline. The crude was extracted with ethyl acetate,
organic layers were dried over magnesium sulfate and
evaporated. Purification by column chromatography
(Petroleum ether-Ethyl acetate, 3/1) yields a yellow oil.
Method B. To 1.1 molar equivalents of the appropriate
alcohol in THF, are added 1.1 equivalents of sodium
hydride (60% in oil). The mixture was heated 1 hour at
60°C. Then, 1 equivalent of 2-chloronicotinoyl chloride
hydrochloride was added, and the mixture was refluxed
overnight. Solvent was removed, and the remaining
product was poured onto water, extracted with ethyl
acetate, dried over magnesium sulfate, and evaporated to
dryness, product was purified by column chromatography
(ethyl acetate).
Typical procedure for Claisen condensation. In a
round bottom flask under argon fitted with a refrigerant,
are placed 2 equivalents of sodium hydride (60% in oil)
and anhydrous THF (100 mL/g NaH). Two equivalents of
NMP in THF (10 mL/g NMP) were added dropwise, and
stirred 30 minutes. One equivalent of the appropriate ester
in THF (10 mL/g ester) is dropped and the mixture was
refluxed overnight. THF was removed under vacuum, and
the crude was poured onto a solution of 6 M HCl. The
aqueous layer was extracted with ethyl acetate, and
neutralized with solid NaHCO3. Then, the aqueous layer
was extracted with ethyl acetate, dried over magnesium
sulfate and evaporated. Purification by column
chromatography on silica gel (EtOAc) affords the final
product.
3-[(6-Methoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolid-
inone (6a). This compound was obtained as a yellow solid
1
Methyl 2-chloronicotinate (5a) [22], Ethyl 2-chloro-
nicotinate (5b) [23], tert-Butyl 2-chloronicotinate (5g)
[24].
(51%). Mp= 89-90°C. H NMR (250 MHz, CDCl3): ꢀ 8.97 (s,
1H), 8.30 (d, 1H, J = 10 Hz), 6.81 (d, 1H, J = 9 Hz), 4.34 (m,
1H), 4.01 (s, 3H), 3.60-3.39 (m, 2H), 2.86 (s, 3H), 2.70-2.25 (m,
2H). 13C NMR (250 MHz, CDCl3): ꢀ 193.7, 169.8, 166.9, 150.9,
139.3, 125.7, 125.9, 110.8, 54.1, 50.5, 48.1, 30.0 21.1. MS (EI):
m/z (%) = 98(57), 136 (100), 191 (27), 234 (28, [M+]). Anal.
Calcd. for C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found: C,
61.55; H, 6.11; N, 11.89.
Propyl 2-chloronicotinate (5c). This compound was
obtained as a yellow oil (51%).1H NMR (250 MHz, CDCl3): ꢀ
8.34 (d, J = 12 Hz, 1H), 8.03 (d, J = 12 Hz, 1H), 7.20 (t, J = 12
Hz, 1H), 4.19 (t, 2H), 1.66 (m, 2H), 0.88 (t, 3H). 13C NMR (250
MHz, CDCl3): ꢀ 164.4, 151.6, 149.6, 140.4, 127.0, 122.1, 67.5,
21.9, 10.4. MS (EI): m/z (%) = 158 (100), 199 (2.1, [M+]). Anal.
Calcd. for C9H10ClN2O: C, 54.15; H, 5.05; N, 7.02. Found: C,
54.21; H, 5.11; N, 6.99.
3-[(6-Ethoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolidin-
one (6b). This compound was obtained as a yellow solid (50%).
1
Mp: 103-105°C. H NMR (250 MHz, CDCl3): ꢀ 8.96 (s, 1H),
Isopropyl 2-chloronicotinate (5d). This compound was
obtained as a yellow oil (55%).1H NMR (250 MHz, CDCl3): ꢀ
8.39 (d, J = 12 Hz, 1H), 8.03 (d, J = 12 Hz, 1H), 7.20 (t, J = 12
Hz, 1H), 5.13 (m, 1H), 1.21 (m, 6H). 13C NMR (250 MHz,
CDCl3): ꢀ 163.9, 151.4, 149.7, 139.8, 127.5, 122.1, 69.8, 21.6.
MS (EI): m/z (%) = 140 (100), 199 (12.4, [M+]). Anal. Calcd. for
C9H10ClN2O: C, 54.15; H, 5.05; N, 7.02. Found: C, 54.25; H,
4.96; N, 7.11.
8.32 (d, 1H, J = 10 Hz), 6.82 (d, 1H, J = 9 Hz), 4.53 (q, 2H),
4.34 (m, 1H), 3.64-3.36 (m, 2H), 2.85 (s, 3H), 2.75-2.16 (m,
2H), 1.39 (t, 3H). 13C NMR (250 MHz, CDCl3): ꢀ 193.7, 169.8,
166.7, 150.9, 139.6, 125.7, 126.9, 110.9, 62.6, 50.4, 47.9, 29.5,
21.2, 14.5. MS (EI): m/z (%) = 122 (100), 150 (76), 205 (50),
248 (25, [M+]). Anal. Calcd. for C13H16N2O3: C, 62.89; H, 6.50;
N, 11.28. Found: C, 62.91; H, 6.55; N, 11.21.
3-[(2-Methoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolid-
inone (7a). This compound was obtained as a yellow oil (47%).
1H NMR (250 MHz, CDCl3): ꢀ 8.23 (d, J = 8 Hz, 1H), 7.99 (d, J
= 10 Hz, 1H), 6.92 (t, J = 9 Hz, 1H), 4.56 (m, 1H), 3.89 (s, 3H),
3.38-3.27 (m, 2H), 2.75 (s, 3H), 2.40-2.20 (m, 2H). 13C NMR
(250 MHz, CDCl3): ꢀ 197.6, 170.5, 161.5, 150.7, 140.1, 121.2,
116.9, 53.6, 53.2, 47.5, 29.2, 21.6. MS (EI): m/z (%) = 136
(100), 234 (19.6, [M+]). Anal. Calcd. for C12H14N2O3: C, 61.53;
H, 6.02; N, 11.96. Found: C, 61.56; H, 5.95; N, 12.01.
3-[(2-Ethoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolidi-
none (7b). This compound was obtained as a yellow oil (46%).
1H NMR (250 MHz, CDCl3): ꢀ 8.28 (d, J = 8 Hz, 1H), 8.03 (d, J
= 10 Hz, 1H), 6.96 (t, J = 9 Hz, 1H), 4.67 (m, 1H), 4.38 (q, 2H),
3.54-3.32 (m, 2H), 2.90 (s, 3H), 2.57-2.25 (m, 2H), 1.35 (t, 3H).
13C NMR (250 MHz, CDCl3): ꢀ 198.3, 171.1, 161.6, 151.1,
140.3, 121.5, 117.1, 62.6, 53.8, 47.9, 29.8, 22.3, 14.6. MS (EI):
m/z (%) = 150 (100), 248 (39.9, [M+]). Anal. Calcd. for
Butyl 2-chloronicotinate (5e). This compound was obtained
as a yellow oil (81%).1H NMR (250 MHz, CDCl3): ꢀ 8.42 (d, J =
12 Hz, 1H), 8.09 (d, J = 12 Hz, 1H), 7.28 (t, J = 12 Hz, 1H), 4.29
(t, J = 13 Hz, 2H), 1.70 (m, 2H), 1.40 (m, 2H), 0.91 (t, J = 14
Hz, 3H). 13C NMR (250 MHz, CDCl3): ꢀ 164.6, 151.7, 149.8,
140.2, 127.2, 122.2, 65.9, 30.5, 19.2, 13.6. MS (EI): m/z (%) =
158 (100), 213 (1.0, [M+]). Anal. Calcd. for C10H12ClN2O: C,
56.21; H, 5.66; N, 6.56. Found: C, 56.29; H, 5.57; N, 6.62.
sec-Butyl 2-chloronicotinate (5f). This compound was
1
obtained as a yellow oil (68%). H NMR (250 MHz, CDCl3): ꢀ
8.44 (d, J = 12 Hz, 1H), 8.07 (d, J = 12 Hz, 1H), 7.27 (t, J = 12
Hz, 1H), 5.10 (m, 1H), 1.96 (m, 2H), 1.36 (d, 3H), 0.88 (t, 3H).
13C NMR (250 MHz, CDCl3): ꢀ 164.2, 151.7, 149.6, 140.1,
127.6, 122.1, 74.5, 28.6, 19.4, 9.9. MS (EI): m/z (%) = 140
(100), 213 (0.6, [M+]). Anal. Calcd. for C10H12ClN2O: C, 56.21;
H, 5.66; N, 6.56. Found: C, 56.25; H, 5.58; N, 6.61.

Jan-Feb 2008
Claisen condensation of N-methylpyrrolidinone and ꢀ-chloronicotinic esters
233
C13H16N2O3: C, 62.89; H, 6.50; N, 11.28. Found: C, 62.94; H,
6.47; N, 11.21.
ester) were added dropwise and the mixture heated at
reflux overnight. THF was removed, and the residue was
poured onto a solution of 6 M HCl. The aqueous layer was
extracted with ethyl acetate, and then neutralized with 4 M
NaOH. Aqueous layer was extracted with ethyl acetate;
and the organic layer was dried over magnesium sulfate
and evaporated. Product was suspended in ether, stirred 15
minutes and filtered, affording 45% of an orange solid.
1-Methyl-3-[(2-propoxy-3-pyridinyl)carbonyl]-2-pyrroli-
dinone (7c). This compound was obtained as a yellow oil
1
(61%-). H NMR (250 MHz, CDCl3): ꢁ 8.26 (d, J = 8 Hz, 1H),
7.83 (d, J = 10 Hz, 1H), 6.77 (t, J = 9 Hz, 1H), 4.52 (m, 1H),
4.21 (t, 2H), 3.33-3.14 (m, 2H), 2.64 (s, 3H), 2.28-2.11 (m, 2H),
1.59 (m, 2H), 0.86 (t, 3H). 13C NMR (250 MHz, CDCl3): ꢁ
198.1, 170.7, 161.5, 150.8, 139.9, 121.3, 116.8, 68.1, 53.5, 29.5,
22.3, 10.4. MS (EI): m/z (%) = 122 (100), 262 (12.6, [M+]).
Anal. Calcd. for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68.
Found: C, 64.19; H, 6.88; N, 10.61.
1
Mp= 165-167°C. H NMR (250 MHz, CDCl3): ꢁ 15.59 (s,
1H), 8.84 (s, 1H), 8.80 (s, 1H), 8.10 (d, J = 9 Hz, 1H), 7.81
(d, J = 8 Hz, 1H), 7.13 (d, J = 8 Hz, 1H), 6.96 (d, J = 9Hz,
1H), 6.00 (s, 1H), 4.20 (m, 1H), 3.50-3.25 (m, 2H), 2.81
(s, 3H), 2.81-2.15 (m, 2H), 2.45 (s, 3H). 13C NMR (250
MHz, CDCl3): ꢁ 192.1, 170.5, 169.4, 159.1, 146.7, 145.5,
136.7, 134.0, 129.7, 125.3, 123.2, 120.9, 93.1, 50.6, 47.9,
29.9, 24.2, 20.7. Calcd. for C19H19N3O3 m/z = 338.149
(M+H). Found m/z = 338.157 (M+H).
3-[(2-Isopropoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrol-
idinone (7d). This compound was obtained as a yellow oil
1
(55%). H NMR (250 MHz, CDCl3): ꢁ 8.26 (d, J = 8 Hz, 1H),
8.02 (d, J = 10 Hz, 1H), 6.88 (t, J = 9 Hz, 1H), 5.41 (m, 1H),
4.58 (m, 1H), 3.52-3.30 (m, 2H), 2.59 (s, 3H), 2.59 (m, 2H),
1.32 (m, 6H). 13C NMR (250 MHz, CDCl3): ꢁ 198.6, 171.2,
161.1, 151.1, 140.3, 121.6, 116.7, 69.2, 53.8, 47.8, 29.7, 22.6,
22.0. MS (EI): m/z (%) = 122 (100), 262 (17.6, [M+]). Anal.
Calcd. for C14H18N2O3: C, 64.10; H, 6.92; N, 10.68. Found: C,
64.16; H, 6.85; N, 10.74.
3-[(2-Butoxy-3-pyridinyl)carbonyl]-1-methyl-2-pyrrolidin-
one (7e). This compound was obtained as a yellow oil (43%). 1H
NMR (250 MHz, CDCl3): ꢁ 8.15 (d, J = 8 Hz, 1H), 7.91 (d, J =
10 Hz, 1H), 6.81 (t, J = 9 Hz, 1H), 4.54 (m, 1H), 4.22 (t, 2H),
3.40-3.19 (m, 2H), 2.71 (s, 3H), 2.27 (m), 2.36-2.19 (m, 2H),
1.40 (m, 2H), 1.31, (m, 2H), 0.86 (t, 3H). 13C NMR (250 MHz,
CDCl3): ꢁ 198.3, 170.8, 161.2, 150.8, 139.9, 121.5, 116.5, 73.5,
53.6, 47.5, 29.4, 28.7, 22.4, 19.1, 9.7. MS (EI): m/z (%) = 122
(100), 276 (11.9, [M+]). Anal. Calcd. for C15H20N2O3: C, 65.20;
H, 7.30; N, 10.14. Found: C, 65.29; H, 7.26; N, 10.20.
Acknowledgement. We thank the Ministère de la
Culture, de l’Enseignement Supérieur et de la Recherche
du Luxembourg, for financial support (BFR), Mrs. V.
Poddig for recording the NMR spectra and Dr. G. Frache
(LSMCL) for performing TOF spectra.
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1
(54%). H NMR (250 MHz, CDCl3): ꢁ 8.19 (d, J = 8 Hz, 1H),
7.95 (d, J = 10 Hz, 1H), 6.86 (t, J = 9 Hz, 1H), 5.13 (m, 1H),
4.59 (m, 1H), 3.45-3.24 (m, 2H), 2.77 (s, 3H), 2.27 (m, 2H),
1.76-1.60 (m, 2H), 1.29 (m, 3H), 0.86 (m, 3H). 13C NMR (250
MHz, CDCl3): ꢁ 198.3, 170.8, 161.2, 150.8, 139.9, 121.5, 116.5,
73.5, 53.6, 47.5, 29.4, 28.7, 22.4, 19.1, 9.7. MS (EI): m/z (%) =
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(48%). 1H NMR (250 MHz, CDCl3): ꢁ 8.20 (d, J = 8 Hz, 1H), 7.93
(d, J = 10 Hz, 1H), 6.84 (t, J = 9 Hz, 1H), 4.57 (m, 1H), 4.30 (t,
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234
T. Kaminski, G. Kirsch
Vol 45
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