Microwave-Assisted Bohlmann-Rahtz Synthesis of Highly Substituted 2-Aminonicotinates

Article abstract of DOI:10.1055/s-0035-1561941

Microwave irradiation of 2-carbethoxyacetamidine and an ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for 1.5 hours facilitated Bohlmann-Rahtz pyridine synthesis to give highly substituted ethyl 2-aminonicotinates with total regiocontrol and in reasonable to excellent yield, following purification by immobilization upon an acidic resin.

Full text of DOI:10.1055/s-0035-1561941

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
M. C. Bagley et al.
Letter
Synlett
Microwave-Assisted Bohlmann–Rahtz Synthesis of Highly Substi-
tuted 2-Aminonicotinates
Mark C. Bagley*
Ayed Alnomsy
Scott J. Temple
Department of Chemistry, School of Life Sciences,
University of Sussex, Falmer, Brighton, East Sussex,
BN1 9QJ, UK
m.c.bagley@sussex.ac.uk
Received: 12.02.2016
Accepted after revision: 03.03.2016
Published online: 30.03.2016
Following its discovery, the Bohlmann–Rahtz pyridine
synthesis received little attention for 40 years, after which
it has seen many applications,2–26 in particular for the syn-
thesis of the 2,3,6-trisubstituted pyridine domain of thio-
peptide antibiotics.3–6 These studies have identified milder
experimental procedures that are regio-, chemo- and even
stereospecific, for potential application in natural product
chemistry and target synthesis, and have provided alterna-
tive processing methods, such as the use of microwave di-
electric heating, microwave flow reactors and continuous
processing to enable the scale up of methodology.2 Yet de-
spite all of these advances, the Bohlmann–Rahtz pyridine
synthesis is still frustrated by essentially the same limited
substrate scope established in the original report1 and so
has only been used for the synthesis of alkyl-, aryl- or het-
eroaryl-substituted pyridines bearing electron-withdraw-
ing groups. Indeed, the presence of an electron-withdraw-
ing group, such as an ester, amide or nitrile, is essential for
enamine 2 stabilization in this process. Some progress has
been made towards the synthesis of 5-bromopyridines
through capture of the aminodienone intermediate 3 with
NBS,27 but the synthesis of electron-rich pyridines by a
Bohlmann–Rahtz approach was unrealized.
DOI: 10.1055/s-0035-1561941; Art ID: st-2016-d0098-l
Abstract Microwave irradiation of 2-carbethoxyacetamidine and an
ethynyl ketone under acidic or basic conditions in ethanol at 150 °C for
1.5 hours facilitated Bohlmann–Rahtz pyridine synthesis to give highly
substituted ethyl 2-aminonicotinates with total regiocontrol and in rea-
sonable to excellent yield, following purification by immobilization
upon an acidic resin.
Key words 2-aminopyridines, heterocycles, ethynyl ketones, micro-
wave synthesis, catch-and-release
Bohlmann and Rahtz first reported the two-step syn-
thesis of trisubstituted pyridines by the reaction of en-
amines 1 and ethynyl ketones or aldehydes, 2, in 1957
(Scheme 1).1 This cyclocondensation process is completely
regioselective and proceeds by Michael addition, enamine
C-functionalization giving a kinetically stable aminodiene
intermediate 3 that can be isolated and purified, before
heating at temperatures of 120–170 °C to promote E/Z-
isomerization and spontaneous cyclodehydration to give
2,3,6-trisubstituted pyridines 4 in good overall yield.
Herein, we describe a new rapid method for the synthe-
sis of 2-aminopyridines using the Bohlmann–Rahtz reac-
tion. Our disconnective scheme approached their synthesis
using methylenediamine 5 in cyclocondensation with an
ethynyl ketone (Scheme 2). 2-Aminonicotinates have been
prepared before from precursor 5 by condensation with di-
carbonyl compounds,28 chromone derivatives,29 chalcones
using ethyl cyanoacetate and ammonium acetate adsorbed
over neutral alumina,30 β-aminovinyl ketones,31 and β-me-
thoxyvinyl ketones, or their corresponding sodio enolates in
the presence of acetic acid, in the synthesis of naphthyri-
dine-3-carboxamides as novel DNA ligase inhibitors.32 Fur-
thermore, related methylenediamines derived from phenyl
EWG
EtOH, ~50 °C
+
H2N
R1
70–95%
O
R2
2 R2 = H, Me,
Ph, n-heptyl
1 R1 = Me, Ph, Tol
EWG = CO2Et,
COMe, CN
O
EWG
R1
120–170 °C
EWG
H2N
R2
vacuum
60–92%
N
R2
R1
3
4
Scheme 1 Two-step pyridine synthesis, as reported by Bohlmann and
Rahtz in 19571
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
M. C. Bagley et al.
Letter
Synlett
cyanomethanesulfonate have been shown33 to give 2-amin-
opyridines in Guareschi–Thorpe-type reactions and so it
was not unreasonable that a similar profile of reactivity
could be promoted for this bisnucleophile in a Bohlmann–
Rahtz process. However, diaminopropenoate 5 could be in
dynamic equilibrium with the carbethoxyacetamidine tau-
tomer (6) and it is known that amidines react readily with
ethynyl ketones under both acidic and basic conditions to
give pyrimidines,34–36 so it was not at all obvious whether
this approach was viable and would proceed through
enamine C-functionalization (path a), to give aminopyri-
dine 7, or N-functionalization (e.g. path b), to give pyrimi-
dine 8, or whether a mixture of products would be ob-
tained. It has long been known that carbethoxyacetamidine
(6) undergoes self-condensation to give the pyrimidine de-
rivative 9 under basic conditions,37 routes to a number of 2-
phenacylpyrimidine derivatives have been described by cy-
clocondensation of benzoylacetamidine,38 and amidine 6
has been reported to give a mixture of pyridine- and pyrim-
idine-containing cyclocondensation products in a 2:3 ratio,
which were difficult to separate, on reaction with a related
prop-2-enylidine biselectrophile.39 Nonetheless, given our
understanding of the Bohlmann–Rahtz reaction, as well as
the precedent that the related hydroacetate salts of imino-
propanoates40 and a range of amidinoacetic esters41 under-
go C-alkylative Michael addition in the synthesis of
Hantzsch dihydropyridines, the Bohlmann–Rahtz reaction
of these derivatives seemed worthy of investigation.
ketone 2a, or substituted derivatives (11a–c) thereof, using
a range of different conditions (Table 1) indicated that Bohl-
mann–Rahtz cyclocondensation was indeed observed to
some extent in all of these acid-mediated methods. Fur-
thermore, only a single pyridine regioisomer was identi-
fied, proposed to be the product of Michael C-addition
(Scheme 2, path a) with spontaneous E/Z-isomerization and
cyclodehydration occurring under the reaction conditions.
A number of trends were noted. High temperature condi-
tions were required and the presence of additional acid
(AcOH) appeared to facilitate the reaction of 4-(trimethylsi-
lyl)butynone 11a (entry 2 vs. 4; entry 5 vs. 6), presumably
by accelerating protodesilylation in accordance with our
previous observations on acid-catalyzed Bohlmann–Rahtz
reactions.20 Despite most procedures appearing to be effec-
tive, from spectroscopic analysis of the crude reaction mix-
tures, the isolated yields of either trisubstituted 7a or tetra-
substituted pyridines 12b,c were always moderate at best,
after purification by column chromatography (Table 1, en-
tries 1–8), with small variation depending upon the sub-
strate. Switching to an alternative isolation method and re-
placing chromatographic purification with immobilization
upon a sulfonic acid resin, a related process which we have
used before for isolating pyridine combinatorial libraries,16
and eluting with alcoholic ammonia (Table 1, entry 9) or al-
coholic aqueous ammonia (Table 1, entry 10), gave an im-
mediate improvement in the isolated yield, even for highly
unreactive substrates (11c; Table 1, entry 10). For butynone
2a, irradiating the mixture at 150 °C for 1.5 hours in the ab-
sence of acetic acid, followed by aqueous workup and im-
mobilization on the resin, gave pyridine 7a in excellent
yield (Table 1, entry 11), demonstrating that the Bohl-
mann–Rahtz synthesis of 2-aminonicotinates was viable
and efficient.
O
2
EtO2C
6
R
EtO2C
5
H2N
NH
self-
NH3
H2N
NH2
O
R
condense EtOH
2
NH2
path a
react at C
path b
react at N
NH4Cl
EtOH
microwaves
2
2
EtO2C
EtO
EtO2C
H2N
N
EtO2C
EtO2C
H2N
N
OH
120 °C, 1 h
78%
N
NH
NH
9
EtO2C
6·HCl
N
R
10·HCl
N
R
K2CO3
95%
7
8
10
Scheme 2 Possible reaction pathways due to tautomerization be-
tween methylenediamine 5 and acetamidine 6
R2
R2
N
6·HCl
EtOH
microwaves
EtO2C
see Table 1
for conditions
H2N
R1
Iminopropanoate hydrochloride 6·HCl was prepared by
a modification of a known route,40,41 adopting microwave-
assisted conditions and avoiding the use of anhydrous HCl
gas, to dramatically shorten reaction times and simplify ex-
perimental procedures. To that end, ethyl imidate hydro-
chloride 10·HCl was transformed to the free base 10 (ob-
served, spectroscopically, as predominantly the enamine
tautomer in CDCl3) and reacted with ammonium chloride
in EtOH under microwave irradiation at 120 °C for one hour
(Scheme 3) to give acetamidine hydrochloride 6·HCl after a
simple trituration. Reaction of amidine 6·HCl with ethynyl
O
R1
2 or 11 R1, R2:
2a Me, H
11a Me, SiMe3
11b Me, Ph
11c Me, Et
7 or 12 R1, R2:
7a Me, H
12a Me, SiMe3
12b Me, Ph
12c Me, Et
Scheme 3 Synthesis of trisubstituted 7 and tetrasubstituted 2-amino-
pyridines 12 using assorted Bohlmann–Rahtz methods
In order to progress towards a method suitable for the
synthesis of pyridine arrays, the optimized microwave-as-
sisted procedure was investigated, with or without the use
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
M. C. Bagley et al.
Letter
Synlett
Table 1 Optimizing Reaction Conditions for the Bohlmann–Rahtz Syn-
proceeding by C-functionalization of diaminopropenoate
tautomer 5 (Scheme 2, path a), followed by cyclodehydra-
tion.
thesis of 2-Aminopyridinesa
Entry
Substrate
Product
Acidb
Conditionsc
Yield (%)
R2
R2
1
2
2a
11a
11a
11a
11a
11a
11b
11c
11a
11c
2a
7a
7a
7a
AcOH
AcOH
AcOH
140 °C, 1 h
140 °C, 1 h
150 °C, 1 h
140 °C, 1 h
reflux,e 24 h
reflux,e 24 h
140 °C, 1 h
140 °C, 1 h
140 °C, 1 h
150 °C, 1.5 h
150 °C, 1.5 h
38
EtO2C
H2N
i) EtOH, microwaves
150 °C, 1.5 h
EtO2C
H2N
+
29
ii) SCX-2; iii) NH3
R1
see Table 2
NH
N
R1
3
33
O
4
7a:12a none
(7:5)d
34
7a,b (R2 = H)
or 12b,c
2a,b (R2 = H)
or 11a–c
6·HCl
5
7a
7a
AcOH
none
AcOH
AcOH
AcOH
AcOH
none
Scheme 4 Acid-mediated Bohlmann–Rahtz synthesis of 2-aminonico-
tinates 7a,b and 12b,c
6
11
7
12b
12c
7a
25
8
12
9
60f
29f
87f
Table 2 Isolated Yields of 2-Aminonicotinates 7a,b and 12b,c from
the Acid-Mediated Bohlmann–Rahtz Reaction of 6·HCl and a Range of
Ethynyl Ketonesa
10
11
12c
7a
a Isolated yields after reaction of amidine 6·HCl (1 equiv) with ethynyl ke-
tone 2a or 11 (1.1–1.7 equiv) under the given conditions in EtOH, followed
by purification by column chromatography on silica, unless stated other-
wise.
Entry
2/11b
R1
R2
7/12c Workupd Yield (%)
1
2
3
4
5
6
7
2a
2a
Me
Me
Me
Me
Me
Me
Ph
H
7a
7a
yes
no
87
b A Brønsted acid (AcOH) was added by carrying out the reaction in EtOH–
AcOH (5:1) under the given conditions, followed by basic workup and puri-
fication by column chromatography on silica, unless stated otherwise.
c The reaction was carried out in a sealed Pyrex™ tube (10 mL) for the given
time (hold time) by microwave irradiation at the specified temperature us-
ing a single-mode microwave synthesizer (CEM Discover®) by moderation
of the initial magnetron power (200 W).
H
82
11c
11a
11b
11b
2b
Et
12c
7a
yes
no
29
SiMe3
Ph
Ph
H
n.d.e
71
12b
12b
7b
yes
no
d Isolated yield not determined as a mixture of trisubstituted pyridine 7a
and tetrasubstituted pyridine 12a was obtained (ratio given in parentheses,
determined by 1H NMR spectroscopic analysis).
71
no
73
e The reaction was carried out under traditional conductive heating in an
open vessel.
a Isolated yield of 2-aminopyridine 7 or 12 after microwave irradiation of
amidine 6·HCl (1 equiv.) and ethynyl ketone 2a or 11 (1.1 equiv) in EtOH in
a sealed Pyrex™ tube at 150 °C for 1.5 h (hold time), by moderation of the
initial magnetron power (200 W). After cooling, the solution was immobi-
lized on a Biotage ISOLUTE SCX-2 column, eluting with EtOH–NH4OH (aq;
35%; 5:1).
f Isolated yield after basic workup, followed by immobilization on a Biotage
ISOLUTE SCX-2 column, eluting with methanolic ammonia (entry 9) or
EtOH–NH4OH (aq; 35%; 5:1; entries 10 and 11).
of an aqueous workup prior to immobilization on SCX-2
resin (Table 2). A small range of ethynyl ketones was stud-
ied (Scheme 4), including the highly reactive butynone 2a
and unreactive hexynone 11c. In related acid-catalyzed
Bohlmann–Rahtz methods, terminally substituted alkynes
retard the Michael addition and so commonly give lower
yields of their respective pyridine products.2,20 A similar
trend was observed for this reaction (Table 2, entry 1 vs. en-
try 3) and the process was still poorly efficient for the unre-
active hexynone 11c (Table 2, entry 3). 4-(Trimethylsi-
lyl)butynone 11a was also not ideal as a substrate in this re-
action as protodesilylation was incomplete under the
chosen conditions (Table 2, entry 4). However, for all of the
other substrates, including 4-phenylbutynone 11b (Table 2,
entries 5 and 6), the reaction was efficient. The use of an
aqueous workup made little difference to the isolated yield
(Table 2, entry 1 vs. entry 2; entry 5 vs. entry 6) and so,
with simple immobilization upon an acidic resin, this ex-
perimental procedure42 would appear to be highly amena-
ble for array production. In all cases only a single pyridine
regioisomer was isolated, in a reaction course that was con-
sistent with the proposed Bohlmann–Rahtz mechanism,2
b Ethynyl ketone 2 (R2 = H) or 11, with substituents R1 and R2 as shown.
c Pyridine product, either trisubstituted 7 (R2 = H) or tetrasubstituted 11,
with substituents R1 and R2 as shown.
d Workup indicates that, after cooling, the mixture was partitioned be-
tween aq NaHCO3 solution and EtOAc. The organic extracts were com-
bined, evaporated in vacuo and immobilized on a Biotage ISOLUTE SCX-2
column, eluting with EtOH–aq NH4OH (5:1).
e Incomplete protodesilylation occurred under the reaction conditions.
In order to understand the chemoselectivity of the pro-
cess, and why it appeared that pyridines rather than pyrim-
idines were produced, conditions which one might expect
would favour pyrimidine production35 were investigated
under microwave irradiation. Amidine hydrochloride 6·HCl
was transformed to the free base 6 (and/or tautomer 5), by
pretreatment with Na2CO3 (Scheme 5), and reacted with six
ethynyl ketones (2a–d and 11b,c), of differing reactivity, in
EtOH at 150 °C (Table 3). After cooling, the reaction mixture
was immobilized directly, as before on a sulfonic acid resin,
then eluted with ethanolic ammonia or aqueous ethanolic
ammonia.43 Surprisingly, the corresponding 2-aminopyri-
dine product44 was isolated in all cases and, for the most
part, in comparable or improved yield (with the exception
of entry 3 in Table 3). This demonstrated a clear reactivity
profile: under microwave irradiation at high temperature,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
M. C. Bagley et al.
Letter
Synlett
carbethoxyacetamidine (6) reacts with a range of ethynyl
ketones in Bohlmann–Rahtz pyridine synthesis, under ei-
ther acidic or basic conditions, to give highly substituted 2-
aminonicotinates in moderate to excellent yield.
Acknowledgment
We thank the EPSRC-BBSRC-MRC sponsored network SMS-Drug
(EP/I037229/1; award to M.C.B.), Saudi Cultural Bureau (support for
A.A.) and the R. M. Phillips Trust (award to M.C.B.) for support of this
work and Dr Alaa Abdul-Sada at the University of Sussex and the EPS-
RC Mass Spectrometry Service at the University of Wales, Swansea
UK, for mass spectra.
O
R2
R2
2 or 11
EtO2C
H2N
R1
EtO2C
H2N
ii) microwaves, 150 °C, 1.5 h
iii) SCX-2; iv) NH3
NH
N
R1
Supporting Information
6·HCl
6 (or 5)
7a–d, 12b,c
52–92% yield
i) Na2CO3, EtOH
Supporting information for this article is available online at
Scheme 5 Base-mediated procedure for the Bohlmann–Rahtz synthe-
sis of 2-aminonicotinates 7a–d and 12b,c
http://dx.doi.org/10.1055/s-0035-1561941.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
References and Notes
Table 3 Isolated Yields of 2-Aminonicotinates 7a–d and 12b,c from
(1) Bohlmann, F.; Rahtz, D. Chem. Ber. 1957, 90, 2265.
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the Base-Mediated Procedurea
Entry
Substrate
Product
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R2
Yield (%)
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1
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2a
2b
7a
7b
Me
Ph
H
H
84
92
52
54
72
71
11b
11c
2c
12b
12c
7c
Me
Ph
Et
H
Me
p-C6H4Cl
p-anisyl
2d
7d
H
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In conclusion, we have demonstrated that 2-carbe-
thoxyacetamidine hydrochloride (6·HCl) may be easily and
rapidly prepared under microwave-assisted conditions,
simply by irradiating a mixture of the ethyl imidate free
base (10) and NH4Cl in EtOH, and can be reacted with a
range of ethynyl ketones by Bohlmann–Rahtz methods un-
der both acidic and basic conditions upon microwave irra-
diation at 150 °C in EtOH for 1.5 hours to give the corre-
sponding highly substituted 2-aminonicotinate in good
yield and with total regiocontrol. Of the new processes that
we have discovered, the base-mediated cyclocondensation
would appear to be the most consistent. The method is
amenable to high-throughput application and incorporates
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Letter
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ethyl 3-amino-3-iminopropionate hydrochloride (6·HCl; 1
equiv) was pretreated with Na2CO3 (1 equiv) for 10 min. After
filtering, the ethynyl ketone (1.05 equiv) was added and the
mixture in EtOH (3.5 mL) was irradiated at 150 °C for 1.5 h (hold
time) in a pressure-rated glass tube (10 mL) using a CEM Dis-
cover microwave synthesizer by moderation of the initial mag-
netron power (200 W). After cooling in a flow of compressed air,
the solution was immobilized on a Biotage ISOLUTE SCX-2
column and eluted with EtOH–NH4OH (aq; 35%; 5:1) or ethano-
lic NH3 (2 M) to give the title compound.
(44) See Supporting Information for detailed experimental proce-
dures and characterization data for known compounds. Ethyl 2-
amino-6-methyl-4-phenylnicotinate (12b) was prepared using
the above procedure,43 with ethyl 3-amino-3-iminopropionate
hydrochloride (6·HCl; 270 mg, 1.62 mmol), 4-phenyl-3-butyn-
2-one (11b; 270 mg, 1.70 mmol) and Na2CO3 (270 mg, 1.62
mmol), in EtOH (3.5 mL), to give the title compound (216 mg,
52%) as a brown solid; mp 139 °C. IR (neat): 3443, 3272, 2977,
(33) Fischer, M.; Troschütz, R. Synthesis 2003, 1603.
(34) Bagley, M. C.; Lin, Z.; Pope, S. J. A. Tetrahedron Lett. 2009, 50,
6818.
1682, 1606, 1582, 1241 cm–1 1H NMR (500 MHz, CDCl3): δ =
.
7.30–7.33 (3 H, 3′-H, 4′-H, 5′-H), 7.20 (m, 2 H, 2′-Η, 6′-H), 6.41
(s, 1 H, 5-H), 6.29 (br s, 2 H, NH2), 3.88 (q, J = 7.1 Hz, 2 H, OCH2),
2.37 (s, 3 H, Me), 0.69 (t, J = 7.1 Hz, 3 H). 13C NMR (125 MHz,
CDCl3): δ = 168.5 (C), 160.3 (C), 158.7 (C), 153.8 (C), 141.5 (C),
127.9 (CH/CH), 127.4 (CH), 115.2 (CH), 104.7 (C), 60.4 (CH2),
24.2 (Me), 13.1 (Me). MS (EI): m/z = 256 [M·+]. HRMS: m/z [M +
H] calcd for C15H17N2O2: 257.1285; found: 257.1278. Ethyl 2-
amino-4-ethyl-6-methylnicotinate (12c) was prepared using
the above procedure,43 with ethyl 3-amino-3-iminopropionate
hydrochloride (6·HCl) (200 mg, 1.26 mmol), 3-hexyn-2-one
(128 mg, 1.32 mmol), and Na2CO3 (200 mg, 1.26 mmol) in EtOH
(3.5 mL), to give the title compound (133 mg, 54%) as a brown
solid; mp 141 °C. IR (neat): 3450, 3269, 3147, 2972, 1686, 1619,
(35) Bagley, M. C.; Hughes, D. D.; Lubinu, M. C.; Merritt, E. A.; Taylor,
P. H.; Tomkinson, N. C. O. QSAR Comb. Sci. 2004, 23, 859.
(36) Bagley, M. C.; Hughes, D. D.; Taylor, P. H. Synlett 2003, 259.
(37) McElvain, S. M.; Tate, B. E. J. Am. Chem. Soc. 1951, 73, 2760.
(38) Roth, B.; Smith, J. M. Jr. J. Am. Chem. Soc. 1949, 71, 616.
(39) Morgentin, R.; Jung, F.; Lamorlette, M.; Maudet, M.; Ménard, M.;
Plé, P.; Pasquet, G.; Renaud, F. Tetrahedron 2009, 65, 757.
(40) Kobayashi, T.; Inoue, T.; Kita, Z.; Yoshiya, H.; Nishino, S.; Oizumi,
K.; Kimura, T. Chem. Pharm. Bull. 1995, 43, 788.
(41) Meyer, H.; Bossert, F.; Horstmann, H. Liebigs Ann. Chem. 1977,
1895.
(42) Typical Procedure for Microwave-Assisted Synthesis of 2-
Aminonicotinates Using Hydrochloride Salt 6·HCl: A solution
of ethyl 3-amino-3-iminopropionate hydrochloride (6·HCl; 1
equiv) and the ethynyl ketone (1.05 equiv) in EtOH (3 mL) was
irradiated at 150 °C for 1.5 h (hold time) in a pressure-rated
glass tube (10 mL) using a CEM Discover microwave synthe-
sizer by moderation of the initial magnetron power (200 W).
After cooling in a flow of compressed air, the solution was
immobilized on a Biotage ISOLUTE SCX-2 column and eluted
with EtOH–NH4OH (aq, 35%; 5:1) to give the title compound.
1586 cm–1 1H NMR (500 MHz, CDCl3): δ = 6.33 (s, 1 H, 5-H),
.
6.19 (br s, 2 H, NH2), 4.33 (q, J = 7.0 Hz, 2 H, OCH2), 2.78 (q, J =
7.0 Hz, 2 H, 4-CH2CH3), 2.30 (s, 3 H, 6-Me), 1.36 (t, J = 7.0 Hz, 3
H, Me), 1.16 (t, J = 7.0 Hz, 3 H, 4-CH2Me). 13C NMR (125 MHz,
CDCl3): δ = 168.3 (C), 160.3 (C), 159.4 (C), 157.2 (C), 114.8 (CH),
104.6 (C), 60.7 (CH2), 28.6 (CH2), 23.9 (Me), 15.1 (Me), 14.0
(Me). HRMS: m/z [M + H] calcd for C11H17N2O2: 209.1285;
found: 209.1282.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E