Highly efficient, environment-friendly, one-pot synthesis of 2-substituted 4-formylimidazoles from 4-acylaminoisoxazoles

Article abstract of DOI:10.1055/s-0034-1379201

A highly efficient and environment-friendly one-pot synthesis of 2-substituted 4-formylimidazoles was accomplished. Raney nickel catalyzed hydrogenation of 4-acylaminoisoxazoles in ethanol, followed by sodium hydroxide promoted recyclization of the ring-opened intermediates, afforded the functionalized imidazoles.

Full text of DOI:10.1055/s-0034-1379201

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 0065–0070
paper
65
F. Gao et al.
Paper
Synthesis
Highly Efficient, Environment-Friendly, One-Pot Synthesis of
2-Substituted 4-Formylimidazoles from 4-Acylaminoisoxazoles
2-Substituted 4-Formylimidazoles from 4-Amidoisoxazoles
Feng Gao*a
H
R
1) H2, Raney-Ni, EtOH
2) NaOH, EtOH
O
N
Xin-Chuan Tiana
Xiao-Xia Qua
Dan Wanga
Dong Pub
O
N
N
one pot
N
H
R
CHO
12 examples up to 93% yield
a Department of Chinese Traditional Herbal, Agronomy College,
Sichuan Agricultural University, No 211, Huimin Road,
Wenjing Region, Chengdu 611130, P. R. of China
+
8
6
2
(
8
8
)
6
2
9
0
8
7
0
gaofeng@sicau.edu.cn
b State Key Laboratory of Biotherapy, Sichuan University,
Chengdu 610041, P. R. of China
Received: 27.07.2014
Accepted after revision: 01.09.2014
Published online: 30.09.2014
2-Substituted 4-formylimidazoles, important interme-
diates in organic and inorganic chemistry, have been used
in the synthesis of bioactive compounds,7d,10 metal–organic
frameworks7a and some important ligands.11 Because of the
basicity of imidazoles, Lewis acid catalyzed Friedel–Crafts
reactions are not possible. Therefore, to synthesize func-
tionalized imidazoles, substituents should be introduced
prior to the imidazole ring formation.12 To the best of our
knowledge, mainly two synthetic methods have been re-
ported for the synthesis of 2-substituted 4-formylimid-
azoles (Scheme 1): a) (Hydroxymethyl)imidazoles have been
synthesized by the cyclization of imino ethers with dihy-
droxyacetone, and subsequent oxidation afforded the corre-
sponding aldehydes;10b b) 2-Aminoimidazoles have been
synthesized by the cyclization reaction of 3-bromo-1,1-di-
methoxypropan-2-one with guanidine, and subsequent
multistep syntheses afforded 2-substituted 4-formylimid-
azoles.13 However, the methods suffer from disadvantages
such as heavy metal oxidation and multistep procedures. In
1987, Reiter reported the synthesis of 1-substituted 4(5)-
acylimidazoles from 4-aminoisoxazoles by palladium on
carbon catalyzed hydrogenation, followed by base-promot-
ed cyclization; however, only one example of a formylimid-
azole in a low yield was reported.14 Furthermore, in Reiter’s
protocol, haloaryl-substituted imidazole-4-carbaldehydes
could not be obtained and the reactions occurred under
high pressure. Several examples of different substituted
acylimidazoles have also been synthesized following
Reiter’s method.15 In our ongoing study of paclitaxel mimics
as anticancer drugs,16 various 2-substituted 4-formylimid-
azoles were needed as synthetic intermediates. Based on
Reiter’s result, we have developed a highly efficient, ‘one-
pot’ method for the synthesis of 2-substituted 4-formylim-
idazoles, in which 4-acylaminoisoxazoles, as the starting
materials, are subjected to Raney nickel catalyzed hydroge-
nation, followed by sodium hydroxide promoted recycliza-
tion (Scheme 1).
DOI: 10.1055/s-0034-1379201; Art ID: ss-2014-h0468-op
Abstract A highly efficient and environment-friendly one-pot synthe-
sis of 2-substituted 4-formylimidazoles was accomplished. Raney nickel
catalyzed hydrogenation of 4-acylaminoisoxazoles in ethanol, followed
by sodium hydroxide promoted recyclization of the ring-opened inter-
mediates, afforded the functionalized imidazoles.
Key words imidazoles, isoxazoles, one-pot synthesis, hydrogenation,
environment-friendly
Imidazoles have always been a hot topic for research in
organic and pharmaceutical chemistry because of their
broad-spectrum bioactivities and synthetic applications.1
Among the drugs containing an imidazole ring, antifungal
drugs such as miconazole and ketoconazole, which block
the biosynthetic pathway of ergosterol by the selective in-
hibition of fungal cytochrome P450, are well known.2 Some
alkaloids also contain an imidazole ring and exhibit many
prominent bioactivities such as antimicrobial activity and
cytotoxicity.1,3 Recently, other diverse, interesting bioactivi-
ties of imidazoles, such as antikinase IspE activity,4 tubulin
depolymerization inhibition5 and anti-cyclooxygenase ac-
tivity,6 have been demonstrated. Moreover, imidazoles are
important precursors of ligands and polymers. Imidazoles
can coordinate to various metal ions, forming various met-
al–organic polymers with complex structures and different
functions.7 Because of the significant bioactivities and syn-
thetic applications of imidazoles, methods for their synthe-
sis have been extensively studied, including the classical
Debus–Radziszewski imidazole synthesis from a diketone,
an aldehyde and ammonia.8 Several new methods for the
synthesis of novel multisubstituted imidazoles have been
reported recently.9
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F. Gao et al.
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Synthesis
pound in a high yield, the reaction conditions were further
optimized; however, the yield significantly decreased when
the temperature of the recyclization step was decreased
from 45 °C to 25 °C, when water was used as the solvent,
and when a weaker base (Na2CO3) was used in ethanol
(Table 1, entries 6–8).
NH
H
R
OMe
N
MnO2
NH3
R
+
O
HO
N
HO
OH
a) previous work
Table 1 Optimization of the Reaction Conditions
O
MeO
Br
Cl
O
O
N
OMe
+
H
N
H
H
N
one pot
N
H
N
R
NH2
N
N
O
N
MeO
1
Cl
NBoc
NH2
CHO
H
MeO
1a
H2N
H2, catalyst
solvent
base
temperature
H
O
O
b) previous work
one pot
N
H
O
NH2
O
N
Cl
1) H2, EtOH
2) NaOH, EtOH
N
H
R
2
Entrya Solvent, baseb
Temp ( °C) Timec (h) Yieldd (%) Yieldd (%)
c) this work
of 2
of 1a
Scheme 1 Strategies for the synthesis of 2-substituted 4-formylimid-
azoles
1
2
3
4
5
6
7
8
EtOH, Na2CO3
EtOH, NaOH
EtOH, NaOH
H2O, NaOH
45
45
45
45
45
25
25
45
6, 6
8, 6
10, 6
6, 6
6, 4
6, 4
6, 8
6, 8
25
20
16
45
92
92
15
92
5
10
8
4-Chloro-N-(isoxazol-4-yl)benzamide (1) was used as
the starting material to optimize the reaction conditions for
the synthesis of 2-(4-chlorophenyl)-4-formyl-1H-imidazole
(1a) (Table 1). First, ethanol was used as the solvent for the
palladium on carbon catalyzed hydrogenation of 1; LC-MS
analysis showed a low yield of intermediate N-(1-amino-3-
oxoprop-1-en-2-yl)-4-chlorobenzamide (2). Further, the
yield of 2 decreased with increasing hydrogenation time
from 6 to 10 hours (Table 1, entries 1–3). When ethanol was
replaced with water, a slight increase in the yield of inter-
mediate 2 was observed (Table 1, entry 4). A careful analysis
of the LC-MS results of the hydrogenation indicated that the
ring-opening reaction of isoxazole 1 was accompanied by
the hydrodechlorination of the aryl substituent, thus af-
32
88e
45
12
35
EtOH, NaOH
EtOH, NaOH
H2O, NaOH
EtOH, Na2CO3
a Entries 1–4: 5% Pd/C was used as the hydrogenation catalyst; entries 5–8:
5% Raney Ni was used as the hydrogenation catalyst.
b Base (2 equiv) was used.
c The first time refers to the hydrogenation reaction (step 1), and the sec-
ond time to the recyclization reaction (step 2).
d LC-MS yields.
e Isolated yield.
fording
a
byproduct, N-(1-amino-3-oxoprop-1-en-2-
Next, we investigated the substrate scope of different N-
substituted 4-acylaminoisoxazoles under the optimized re-
action conditions [H2, 5% Raney Ni, NaOH (2 equiv), EtOH]
(Table 2). The desired product could be obtained in high
yield when the substituent was an aromatic group (Table 2,
entries 1–11), while the yield significantly decreased when
the substituent was an alkyl group (Table 2, entry 12).
These results can be attributed to the fact that an aromatic
group extends the π-conjugation of the system, thus stabi-
lizing the corresponding intermediate and product. More-
over, the electronic nature of the substituents on the ben-
zene ring also slightly affected the yield: the yields were
slightly decreased with electron-withdrawing substituents
(Table 2, entries 8–10) compared to electron-donating sub-
stituents (Table 2, entries 4 and 5). Further investigations
yl)benzamide. Therefore, the catalyst for the hydrogenation
reaction was changed from palladium on carbon to Raney
nickel, which successfully avoided the dehalogenation reac-
tion, thus affording the key intermediate 2 in 92% yield. Un-
der the alkaline conditions (NaOH, EtOH), the primary ami-
no group of compound 2 attacks the carbonyl of the amide
group to afford the corresponding Schiff base, thus giving
the imidazole ring after dehydration. Next, sodium hydrox-
ide (2 equiv) was added directly into the reaction mixture
after removal of the hydrogenation catalyst by filtration.
LC-MS analysis showed a complete conversion of interme-
diate 2 after 4 hours at 45 °C to afford 2-(4-chlorophenyl)-
4-formyl-1H-imidazole (1a) in 88% isolated yield (Table 1,
entry 5). After the successful synthesis of the desired com-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 65–70

67
F. Gao et al.
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Synthesis
Table 2 (continued)
Entry Starting material
O
revealed no significant difference occurring during the hy-
drogenation reaction, while the yields of the reactions of
the substrates with electron-withdrawing substituents at
the para position of the aromatic ring decreased after the
second step, recyclization, under alkaline conditions. The
electron-withdrawing effect may increase the electroposi-
tivity of the carbonyl carbon on the amide group, thus facil-
itating the formation of a Schiff base. This indicates that the
rate-limiting step of the recyclization reaction is the dehy-
dration of the 2,3-dihydroimidazole. The electron-donating
substituents may facilitate the dehydration reaction, thus
affording the final products in high yields.
Product
O
NH
NH
O
N
N
H
N
7
H
CF3
CF3
7a (84%)
7
O
O
O
O
O
N
N
H
F
F
N
H
8
Table 2 One-Pot Synthesis of 2-Substituted 4-Formylimidazoles from
F
4-Acylaminoisoxazolesa
F
8a (78%)
8
O
Entry Starting material
Product
NH
O
F
F
N
O
O
N
H
N
H
NH
O
N
9
N
H
N
1
H
F
F
9a (79%)
9
Cl
Cl
1a (88%)
1
O
NH
NH
O
O
F
F
O
O
N
NH
NH
NH
O
Cl
Cl
N
N
H
F
F
N
H
10
11
12
N
H
N
H
2
3
10a (80%)
10
2a (85%)
2
O
O
O
O
N
O
O
O
N
N
H
N
H
N
H
Cl
Cl
N
H
N
N
11a (93%)
11
3a (87%)
3
O
O
NH
O
O
N
N
N
H
N
H
N
H
N
H
4
5
6
12a (65%)
12
OMe
OMe
OMe
OMe
a Reaction conditions: H2, 5% Raney Ni, NaOH (2 equiv), EtOH.
4a (90%)
4
O
O
O
NH
NH
O
O
N
N
Finally, we scaled up the reaction with N-(isoxazol-4-
yl)-4-methoxybenzamide (4) to a 100-mmol scale. The de-
sired product, 4-formyl-2-(4-methoxyphenyl)-1H-imid-
azole (4a), was obtained in 85% yield (Scheme 2).
In summary, we have developed a novel, one-pot meth-
od for the synthesis of 2-substituted 4-formylimidazoles. In
this method, 4-acylaminoisoxazoles are used as the starting
materials. Raney nickel catalyzed hydrogenation of the 4-
acylaminoisoxazoles in ethanol affords the ring-opened in-
termediates. Sodium hydroxide promoted, Schiff base cy-
clization of the intermediate in the same pot results in an
imidazole ring after dehydration, thus finally affording the
H
N
H
5a (93%)
5
O
N
N
H
N
H
OCF3
OCF3
6a (85%)
6
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F. Gao et al.
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Synthesis
2-(3-Chlorophenyl)-4-formyl-1H-imidazole (3a)10a
MeO
O
O
N
White amorphous powder; yield: 17.9 mg (87%); mp 152–153 °C.
1H NMR (400 MHz, DMSO-d6): δ = 13.58 (s, 1 H), 9.78 (s, 1 H), 8.15 (s,
1 H), 8.12 (s, 1 H), 8.03 (d, J = 6.8 Hz, 1 H), 7.52 (m, 2 H).
13C NMR (100 MHz, DMSO-d6): δ = 183.2, 147.5, 133.6, 131.4, 130.8,
129.9, 129.1, 128.1, 125.4, 124.3.
1) H2, Raney-Ni, EtOH
2) NaOH, EtOH
H
N
H
N
one pot
N
MeO
4
CHO
4a
17.1 g (85%)
21.8 g (100 mmol)
HRMS (ESI): m/z [M + H+] calcd for C10H8ClN2O: 207.0325; found:
207.0331.
Scheme 2 Scaled-up synthesis of 4-formyl-2-(4-methoxyphenyl)-1H-
imidazole (4a)
4-Formyl-2-(4-methoxyphenyl)-1H-imidazole (4a)10a
2-substituted 4-formylimidazole in high yield. Because this
method is highly efficient and eco-friendly, it can be used
for the rapid synthesis of 4-formylimidazole derivatives
with different aromatic substituents at the C-2 position of
the imidazole ring. Further studies in this direction are un-
derway in our laboratory.
White solid; yield: 18.2 mg (90%); mp 167–168 °C.
1H NMR (400 MHz, CD3OD): δ = 9.74 (s, 1 H), 7.94 (s, 1 H), 7.90 (d, J =
8.8 Hz, 2 H), 7.03 (t, J = 8.8 Hz, 2 H), 3.85 (s, 3 H).
13C NMR (100 MHz, CD3OD): δ = 183.2, 162.7, 152.2, 129.0, 128.0,
122.6, 115.4, 115.2, 55.9.
HRMS (ESI): m/z [M + H+] calcd for C11H11N2O2: 203.0821; found:
203.0832.
1H and 13C NMR spectra were obtained in CDCl3, CD3OD or DMSO-d6
with TMS as the internal standard on a Varian Unity Inova 400/54
spectrometer. Mass spectra were obtained on a VG Auto Spec 3000 or
a Finnigan MAT 90 instrument. IR spectra were obtained with KBr
plates using a Perkin-Elmer Spectrum 1600 Series spectrometer.
Melting points were determined on a Thomas Hoover Unimelt melt-
ing point apparatus and are uncorrected. Silica gel H (Qingdao Sea
Chemical Factory, Qingdao, China) was used for column chromatogra-
phy. Spots on TLC (silica gel G) were detected by UV light. Commer-
cially available reagents and solvents were directly used without fur-
ther purification.
4-Formyl-2-(3-methoxyphenyl)-1H-imidazole (5a)
White solid; yield: 19.2 mg (93%); mp 172–173 °C.
IR (thin film): 3436, 3025, 1565, 1502, 843, 752, 723 cm–1
1H NMR (400 MHz, CD3OD): δ = 9.69 (s, 1 H), 7.96 (s, 1 H), 7.60 (s, 1
H), 7.57 (d, J = 8.0 Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 6.93 (dd, J1 = 8.0 Hz,
J2 = 2.4 Hz, 1 H).
13C NMR (100 MHz, CD3OD): δ = 184.3, 161.5, 154.3, 141.5, 136.6,
133.4, 130.9, 119.6, 116.4, 112.4, 55.8.
MS (ESI): m/z = 203.2 [M + H+].
.
HRMS (ESI): m/z [M + H+] calcd for C11H11N2O2: 203.0821; found:
2-Substituted 4-Formylimidazoles; General Procedure
203.0838.
A 4-(acylamino)isoxazole (0.1 mmol) was hydrogenated under hydro-
gen (balloon) over Raney Ni (5% by weight) in EtOH (ca. 10 mL per
mmol of isoxazole). The reaction was usually finished after 1 h, as de-
termined by TLC (hexane–EtOAc, 2:1); then, the catalyst was removed
by filtration and washed with EtOH. The combined EtOH layer con-
taining the intermediate N-(1-amino-3-oxoprop-1-en-2-yl)amide
was treated with NaOH (2 equiv) at 45 °C for 4 h. Then, the solvent
was removed under reduced pressure and the residue was purified by
chromatography on silica gel (hexane–EtOAc, ca. 4:1, v/v) to give the
desired product.
4-Formyl-2-[4-(trifluoromethoxy)phenyl]-1H-imidazole (6a)
White solid; yield: 20.9 mg (85%); mp 171–172 °C.
IR (thin film): 3424, 3112, 1448, 822, 746, 720 cm–1
1H NMR (400 MHz, CD3OD): δ = 14.38 (s, 1 H), 10.59 (s, 1 H), 8.99 (br
s, 3 H), 8.31 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CD3OD): δ = 187.3, 151.6, 131.3, 130.5, 130.5,
.
126.5, 124.1, 124.1, 124.0, 121.4, 118.9.
MS (ESI): m/z = 257.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C11H8F3N2O2: 257.0538; found:
2-(4-Chlorophenyl)-4-formyl-1H-imidazole (1a)10a
White amorphous powder; yield: 18.1 mg (88%); mp 142–143 °C.
1H NMR (400 MHz, DMSO-d6): δ = 9.79 (s, 1 H), 8.00 (s, 1 H), 7.96 (d,
J = 8.4 Hz, 2 H), 7.51 (d, J = 8.4 Hz, 2 H).
257.0544.
4-Formyl-2-[4-(trifluoromethyl)phenyl]-1H-imidazole (7a)
13C NMR (100 MHz, DMSO-d6): δ = 183.8, 150.7, 140.2, 137.0, 130.2,
White solid; yield: 20.1 mg (84%); mp 168–169 °C.
129.1, 128.9, 127.9.
HRMS (ESI): m/z [M + H+] calcd for C10H8ClN2O: 207.0325; found:
207.0339.
IR (thin film): 3411, 1552, 1418, 1140, 1092, 750 cm–1
1H NMR (400 MHz, CD3OD): δ = 10.61 (s, 1 H), 9.07 (d, J = 8.0 Hz, 2 H),
8.99 (s, 1 H), 8.67 (d, J = 8.0 Hz, 2 H).
.
13C NMR (100 MHz, CD3OD): δ = 186.1, 142.4, 136.0, 135.2, 131.9 (q),
129.0, 129.0, 128.5 (q), 128.5 (q), 128.1, 125.4.
MS (ESI): m/z = 241.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C11H8F3N2O: 241.0589; found:
2-(2-Chlorophenyl)-4-formyl-1H-imidazole (2a)10a
White amorphous powder; yield: 17.5 mg (85%); mp 145–147 °C.
1H NMR (400 MHz, CD3OD): δ = 9.83 (s, 1 H), 8.05 (s, 1 H), 7.74 (s, 1
H), 7.57 (s, 1 H), 7.48 (br s, 2 H).
13C NMR (100 MHz, CD3OD): δ = 184.5, 148.9, 140.5, 133.8, 132.8,
241.0598.
132.5, 132.0, 131.4, 130.1, 128.4.
HRMS (ESI): m/z [M + H+] calcd for C10H8ClN2O: 207.0325; found:
207.0336.
2-(3,5-Difluorophenyl)-4-formyl-1H-imidazole (8a)
White solid; yield: 16.2 mg (78%); mp 152–153 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 65–70

69
F. Gao et al.
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Synthesis
IR (thin film): 3502, 1548, 1420, 1088, 742 cm–1
1H NMR (400 MHz, CD3OD): δ = 9.80 (s, 1 H), 8.02 (s, 1 H), 7.60 (s, 1
.
Acknowledgment
This research was supported by the NSFC (No. 81001383) and the
Doctoral Foundation of the Ministry of Education of China (No.
20105103120009).
H), 7.59 (s, 1 H), 7.06 (s, 1 H).
13C NMR (100 MHz, CD3OD): δ = 184.2, 166.1, 163.6, 149.0, 140.8,
133.6 (t), 133.2, 110.2 (q), 109.2 (d), 105.9 (t).
MS (ESI): m/z = 209.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C10H7F2N2O: 209.0526; found:
Supporting Information
209.0533.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379201.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
2-(2,5-Difluorophenyl)-4-formyl-1H-imidazole (9a)
White solid; yield: 16.4 mg (79%); mp 150–151 °C.
IR (thin film): 3498, 1546, 1418, 1088, 866, 740 cm–1
References
.
1H NMR (400 MHz, CDCl3): δ = 9.77 (s, 1 H), 7.97 (m, 1 H), 7.83 (s, 1
H), 7.07 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 177.5, 159.2, 156.8, 156.0, 153.8,
139.1, 117.5, 116.6, 116.4, 114.7.
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MS (ESI): m/z = 209.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C10H7F2N2O: 209.0526; found:
209.0538.
2-(2,3-Difluorophenyl)-4-formyl-1H-imidazole (10a)17
(6) Assadieskandar, A.; Amirhamzeh, A.; Salehi, M.; Ozadali, K.;
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White solid; yield: 16.6 mg (80%); mp 159–160 °C.
1H NMR (400 MHz, CD3OD): δ = 9.72 (s, 1 H), 7.95 (s, 1 H), 7.69 (t, J =
8.4 Hz, 1 H), 7.29 (q, J = 8.4 Hz, 1 H), 7.20 (m, 1 H).
13C NMR (100 MHz, CD3OD): δ = 184.8, 153.4 (d), 150.8 (q), 148.1 (d),
145.1, 141.3, 131.7, 126.3 (q), 125.7, 119.6 (d).
HRMS (ESI): m/z [M + H+] calcd for C10H7F2N2O: 209.0526; found:
209.0544.
4-Formyl-2-(pyridin-3-yl)-1H-imidazole (11a)
(8) Hu, B.; Wang, Z.; Ai, N.; Zheng, J.; Liu, X.-H.; Shan, S.; Wang, Z.
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White solid; yield: 16.1 mg (93%); mp 135–136 °C.
IR (thin film): 1575, 1451, 1429, 1023, 843, 786, 752, 697 cm–1
1H NMR (400 MHz, CD3OD): δ = 9.54 (s, 1 H), 9.10 (s, 1 H), 8.34 (dd,
J1 = 4.8 Hz, J2 = 1.2 Hz, 1 H), 8.31 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1 H), 7.85
(s, 1 H), 7.35 (dd, J1 = 8.0 Hz, J2 = 4.8 Hz, 1 H).
13C NMR (100 MHz, CD3OD): δ = 184.7, 154.3, 148.9, 147.9, 143.6,
140.4, 135.3, 131.5, 125.2.
MS (ESI): m/z = 174.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C9H8N3O: 174.0667; found:
.
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174.0679.
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4-Formyl-2-isobutyl-1H-imidazole (12a)
White powder; yield: 10.0 mg (65%); mp 110–112 °C.
IR (thin film): 3008, 1481, 1428, 1411, 1143, 1006, 727 cm–1
1H NMR (400 MHz, CD3OD): δ = 10.42 (s, 1 H), 8.67 (s, 1 H), 3.32 (d, J =
7.6 Hz, 2 H), 2.85 (m, 1 H), 1.68 (d, J = 7.2 Hz, 6 H).
13C NMR (100 MHz, CD3OD): δ = 184.7, 154.7, 135.6, 127.7, 39.4, 30.3,
.
24.8.
MS (ESI): m/z = 153.2 [M + H+].
HRMS (ESI): m/z [M + H+] calcd for C8H13N2O: 153.1028; found:
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