Synthesis of (±)- cis -clavicipitic acid by a Rh(I)-catalyzed intramolecular imine reaction

Article abstract of DOI:10.1021/jo500245s

A new and short synthesis of racemic cis-clavicipitic acid was achieved by taking advantage of the double nucleophilic character of indole-4-pinacolboronic ester. Key to the success of the synthesis were an efficient and selective C-3 indole Friedel-Craft

Full text of DOI:10.1021/jo500245s

Note
pubs.acs.org/joc
Synthesis of ( )-cis-Clavicipitic Acid by a Rh(I)-Catalyzed
Intramolecular Imine Reaction
Francesca Bartoccini, Mariangela Casoli, Michele Mari, and Giovanni Piersanti*
Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Piazza del Rinascimento 6, 61029 Urbino (PU), Italy
S
* Supporting Information
ABSTRACT: A new and short synthesis of racemic cis-
clavicipitic acid was achieved by taking advantage of the double
nucleophilic character of indole-4-pinacolboronic ester. Key to
the success of the synthesis were an efficient and selective C-3
indole Friedel−Crafts alkylation and the development of an
unprecedented intramolecular rhodium-catalyzed 1,2-addition
of an aryl pinacolboronic ester to an unactivated imine.
ungi utilize tryptophan and prenyl moieties to form
Fnumerous natural molecules with diverse chemical
structures and intriguing biological and pharmacological
activities.1 These compounds are usually derived from L-
tryptophan or derivatives thereof as backbones and prenyl
moieties as modifications.2 A subset of this class of molecules
containing the unusual azepinoindole tricyclic subunit presents
a unique structural challenge that attracted our attention
(Figure 1).
Brønsted and/or Lewis acids (Scheme 1). These reactions
afforded the desired product as approximately equal mixtures of
cis and trans isomers and consisted of many classical synthetic
procedures. Very recently, Jia et al. reported an elegant
approach to clavicipitic acid in which the synthesis of 4-
substituted tryptophan was obtained by direct olefination at the
C-4 position of protected tryptophan derivatives via C−H
activation using 1,1-dimethylallyl alcohol as the terminal
olefin.7i
We report herein a strategically distinct approach to 1, which
is enabled by an unprecedented Rh(I)-catalyzed intramolecular
1,2-addition of an aryl pinacolboronic ester to an unactivated
imino group as the key carbon−carbon forming step.8
Retrosynthetically, we envisioned that the tricyclic framework
of 1 (Scheme 1) could arise from a late-stage intramolecular
Rh-catalyzed hydroarylation on the imine, obtained by
condensation of unprotected 4-boronated tryptophan methyl
ester (5) and prenal (6) as a suitable five-carbon unit. In view
of the stereochemical and structural complexity of 1, this
powerful disconnection of the natural product presented an
opportunity to highlight the utility of prenal as a surrogate for
1,1-dimethylallyl alcohol to introduce the dimethylallyl unit
into a natural product. The unprotected and racemic 4-
boronated tryptophan methyl ester (5) could, in turn, easily
arise from the Friedel−Crafts alkylation of 4-boronate indole
(2) and 2-amidoacrylate.9 Basically, we recognized the double-
nucleophilic character of the C-3 and the C-4 carbon equipped
with the boryl group of indole 2 and opted to investigate the
possibility of chemoselective transformations of nucleophilic
C−B bonds. It must be stressed that, even if Pictet−Spengler
condensation between L-tryptophan methyl ester and prenal 6
under acidic conditions has been developed,10 related trans-
formations giving regio- and chemoselective 3,4-fused indoles
are, to the best of our knowledge, unprecedented.11
Figure 1. Structures of naturally occurring indole-annulated nitrogen-
containing seven-membered rings.
In particular, the ergot alkaloid biosynthesis derailment
product clavicipitic acid (1) was first isolated from the
Claviceps strain SD58 and from Claviceps fusiformis as a
mixture of cis and trans diastereoisomers, the proportions of
which depend on the specific microorganism from which it is
isolated.3 Together with aurantioclavine,4 it is a member of the
large family of 3,4-ring-fused indole alkaloids characterized by a
nitrogen-containing seven-membered ring5 and has emerged as
a target of interest not only for its intriguing molecular
architecture but also for its proposed role as an intermediate in
the biosynthesis of complex polycyclic alkaloids of the
communesin family.6 Nearly all of the previous synthetic
pathways7 share a common scheme, which involves the
construction of the azepinoindole ring system via a
palladium(0)-catalyzed Heck−Mizoroki reaction of protected
4-halotryptophan derivatives with 1,1-dimethylallyl alcohol,
followed by intramolecular aminocyclization catalyzed by
Received: January 31, 2014
Published: March 7, 2014
© 2014 American Chemical Society
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Note
Scheme 1. Retrosynthetic Analysis of ( )-Clavicipitic Acid (1)
Our approach commenced with the synthesis of 4-boronated
tryptophan methyl ester (4) by Lewis acid mediated Friedel−
Crafts alkylation of the easily accessible and commercially
available 4-boronated indole (2) and methyl 2-(diphenyl-
methyleneamino)acrylate (3) in excellent yield with high regio-
and chemoselectivity (Scheme 2).12 Acrylate 3 was chosen
1,2-addition using a palladium(II) catalyst. However, con-
version of boronic ester 5 to the corresponding boronic acid
and subsequent exposure to different kinds of palladium(II)
salts and complexes led only to deborylation with very low
conversion, probably due to the slow transmetalation step of
the arene from boron to the palladium complex.16a We then
considered the possibility of effecting this transformation using
rhodium catalysis, knowing the more nucleophilic nature of
arylrhodium species compared with that of arylpalladium
species.16d We also decided to use pinacolboronic ester, 5,
which would be expected to be more robust and easier to
synthesize, handle, and purify than the corresponding acid, but
still reactive for subsequent arylation by a rhodium catalyst.16b,c
The reaction conditions for the intramolecular hydroarylation
of 7 are summarized in Table 1.
Scheme 2. Formation of 4-Pinacolboronate Tryptophan
Methyl Ester
The combined use of a chlororhodium complex [{RhCl-
(cod)}2] and bases such as KOH and K3PO4, which are often
used in the rhodium-catalyzed addition of arylboron reagents,
provided very low catalytic activity in the present arylation
(entries 1 and 2).
A better yield and a shorter reaction time were obtained
using CsF as the base/additive (entry 3), probably accelerating
the transmetalation step and enhancing the nucleophilicity of
the arylrhodium species. Furthermore, we found that dioxane,
which is generally used as the solvent in this reaction,17 could
be replaced by the nontoxic solvent dimethoxyethane (DME).
NMR analysis of the crude reaction mixture revealed two major
byproducts in addition to the desired tricyclic azepinoindole 8,
the corresponding phenol and protodeboronation and/or
protodemetalation products resulting from deborylation of
the boronic ester under the reaction conditions, a catalytic dead
end for the C−C coupling step. Although detected in the LC-
MS of the crude reaction mixture, no intermolecular product or
homocoupling product was ever isolated or detected by NMR
analysis, thus suggesting that <5% was formed. These results
prompted us to use a more efficient dimeric rhodium complex
for transmetalation with the arylboronic acid derivative, i.e.,
[Rh(OH)(cod)]2 (entry 4).18 Further studies demonstrated
that the phosphine ligand (dppp) was unnecessary for the
promotion of arylation,19 whereas CsF was required to
maintain the reactivity (entries 5 and 6). No cyclization
product was obtained when KHF2 was added, suggesting that
intramolecular hydroarylation proceeds without formation of
the aryl trifluoroborate (entry 7). After screening various
conditions,20 we were delighted to find that treatment of 5 with
among other available acrylates based on its reported good
reactivity as well as the mild and selective reaction conditions
required for the deprotection of the amino group in the final
compound. Indeed, the benzophenone imine moiety of 4 was
selectively hydrolyzed under acidic conditions. The best
conditions found involved the treatment of 4 with 1 M
HCl−THF (0 °C to RT, 2 h) to afford 5 in 74% yield. The
Friedel−Crafts alkylation/hydrolysis reaction sequence could
be performed routinely on a multigram scale.
With a robust route to aminoboronate 5 secured, we next
explored the condensation of 5 with prenal (6) (Table 1). As
anticipated, condensation of amine 5 with prenal produced the
imine 7 as a stable entity. Initial attempts to cyclize pinacolyl
boronate 5 using the Petasis13 protocol with prenal in
1,1,1,3,3,3-hexafluoro-2-propanol as the solvent14 only pro-
duced the formation of imine 7.15 Importantly, no regular
Pictet−Spengler product was detected in the course of this
reaction, even with different solvents or microwave irradiation.
Encouraged by the precedent set by Lu et al., Lam et al., and
Sarpong et al.16 using the intramolecular transition-metal-
catalyzed addition of arylboronic acids and aryl pinacolboronic
esters to ketones, we began to investigate achieving the desired
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Table 1. Some Examples for the Optimization of the Reaction Conditions for the Intramolecular Rhodium-Catalyzed
Hydroarylation
a
b
c
entry
catalyst/base
solvent
T (°C)/t (h)
yield (%)
dr (8a/8b)
1
2
3
4
5
6
7
[RhCl(cod)]2/dppp/K3PO4
[RhCl(cod)]2/dppp/KOH
[RhCl(cod)]2/dppp/CsF
[Rh(OH)cod]2/dppp/CsF
[Rh(OH)cod]2/CsF
dioxane
dioxane
DME
DME
DME
DME
DME
DME
80/60
80/60
85/48
85/48
85/16
85/16
85/60
85/16
9
18
25
41
55
nd
nd
nd
nd
100/0
[Rh(OH)cod]2
[Rh(OH)cod]2/KHF2
[Rh(OH)cod]2/CsF
d
8
63
100/0
a
Reaction conditions: 5 (0.1 mmol), solvent (0.8 mL), 4 Å molecular sieves (MS) (100 mg), and 6 (0.11 mmol) at RT for 4 h, followed by rhodium
b
c
catalyst (10 mol %), additive (3 equiv), and ligand (20 mol %). Yield of isolated product. Diastereoisomeric ratio determined by analysis of the
crude H NMR with comparison to reported spectra. After imine formation, DME (1.2 mL) was added. nd = not determined; pin = pinacolyl;
d
1
DME = dimethoxyethane.
prenal (1.1 equiv) in DME and 4 Å molecular sieves at 23 °C
for 2 h, followed by the addition of more DME to bring the
solution to a final concentration of 0.05 M, CsF (3 equiv), and
10 mol % [{Rh(OH)(cod)}2] efficiently executed the 1,2-
addition to form the azepine moiety 8 in 63% yield with
complete cis diastereoselectivity (entry 8). At the moment, we
do not have any evidence or explanations regarding the reasons
for this high cis-diastereoselectivity. We are currently under-
going studies to clarify the exact mechanism of the reaction.21
To the best of our knowledge, this is the first example of the
addition of an aryl pinacolboronic ester species to an unactivated
imine using Rh(I) catalysis. The NMR spectra were identical to
those reported and revised for the synthetic cis-clavicipitic acid
methyl ester.7h Alkaline hydrolysis of the ester 8a provided
( )-cis-clavicipitic acid (1a) in 81% yield, according to the
literature procedure (Scheme 3).7a
position (C-4) of the indole core, instead of at the highly
nucleophilic positions C-2 and C-3,22 thanks to the proper
choice of easily handled pinacolboronic ester as the latent
nucleophilic handle in the 1,2-addition reaction.
EXPERIMENTAL SECTION
■
General Methods. All reactions were run in air unless otherwise
noted. Column chromatography purifications were performed in flash
conditions using 230−400 mesh silica gel. Analytical thin layer
chromatography (TLC) was carried out on silica gel plates (silica gel
60 F254) that were visualized by exposure to ultraviolet light and an
aqueous solution of cerium ammonium molybdate (CAM), p-
anisaldehyde, or ninhydrin. 1H NMR, 13C NMR, and 11B NMR
spectra were recorded at 200/50/64 MHz on a spectrometer, using
CDCl3, DMSO-d6, or CD3OD as solvent. Chemical shifts (δ scale) are
reported in parts per million (ppm) relative to the central peak of the
solvent. Coupling constants (J values) are given in hertz (Hz). In 13C
NMR, carbon adjacent to boron was not observed.23 Molecular ions
(M + 1) or (M − 1) are given for ESI-MS analysis. Optical
absorbances are reported in cm−1 for the IR analysis. Melting points
were determined using a capillary melting point apparatus and are
uncorrected. Elemental analyses were within 0.4 of the theoretical
values (C, H, N). 4-Bromo-1H-indole, 4,4,4′,4′,5,5,5′,5′-octamethyl-
2,2′-bi(1,3,2-dioxaborolane) (B2pin2), serine methyl ester hydro-
chloride, and 3-methylbut-2-enal (6) are commercially available. 4-
(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole11 (2) and
methyl 2-(diphenylmethyleneamino)acrylate24 (3) were synthesized
according to the literature procedure.
Scheme 3. Final Hydrolysis to the Natural Product
Methyl 2-(Diphenylmethyleneamino)-3-(4-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate (4).
To a solution of 2 (3 g, 12.3 mmol) and methyl 2-(diphenyl-
methyleneamino)acrylate (3) (2.7 g, 10.2 mmol) in CH2Cl2
anhydrous (50 mL) was added dropwise 1 M EtAlCl2 in hexane
(10.2 mL, 10.2 mmol), at −15 °C, under argon. The solution was
stirred at −15 °C for 30 min and then at room temperature for 2 h.
The mixture was diluted with CH2Cl2 (50 mL), and a saturated
solution of NaHCO3 (100 mL) was added. The resulting suspension
was filtered over Celite and washed with CH2Cl2 (3 × 30 mL). The
two layers were separated, and the aqueous phase was extracted with
further CH2Cl2 (2 × 30 mL). The combined organic phases were
washed with brine and dried over anhydrous Na2SO4, and the solvent
In summary, the concise total synthesis of ( )-cis-clavicipitic
acid (1a), a 3,4-fused-indole alkaloid carrying a prenyl
substituent at the C-4 position, was achieved in only four
total steps from 4-boronate indole (2) with high diaster-
eoselectivity. Key to the completion of the synthesis were a
selective Friedel−Crafts alkylation and an unprecedented
intramolecular Rh(I)-catalyzed imine hydroarylation reaction
via a one-pot procedure. This diastereoselective intramolecular
rhodium-catalyzed “normal” prenylation of tryptophan allowed
the regioselective introduction of the prenyl side chain at C-4 of
tryptophan, forming a C−C bond at the least nucleophilic
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Note
was evaporated under reduced pressure. The residue was purified by
flash chromatography on deactivated silica gel (silica gel was
deactivated by flushing with 1% TEA in cyclohexane/EtOAc 8:2 and
then was washed with cyclohexane/EtOAc 8:2 prior to use) to give 4.7
g (9.3 mmol) of 4 as a pale-yellow solid. Yield 91%. TLC
(cyclohexane/EtOAc 8: 2 + 0.1% TEA), Rf = 0.24 (UV, CAM, p-
anisaldehyde); MS (ESI) 509 [M + H]+; 1H NMR (200 MHz, CDCl3)
δ 1.20 (s, 6H), 1.23 (s, 6H), 3.31 (dd, J1 = 14.0, J2 = 10.5 Hz, 1H),
3.78 (s, 3H), 4.00 (dd, J1 = 14.0, J2 = 3.0 Hz, 1H), 4.63 (dd, J1 = 10.5,
J2 = 3.0 Hz, 1H), 6.25 (br s, 1H), 6.86 (t, J = 7.5 Hz, 2H), 7.06−7.17
(m, 4H), 7.25−7.43 (m, 4H), 7.53−7.57 (m, 3H), 7.99 (br s, 1H); 13C
NMR (50 MHz, CDCl3) δ 24.3, 24.8, 26.9, 51.9, 65.5, 83.2, 113.4,
114.2, 120.6, 125.6, 127.5, 127.6, 127.7, 127.9, 128.7, 129.3, 130.0,
130.4, 135.8, 136.2, 139.6, 170.8, 173.1 (carbon adjacent to boron was
not observed); 11B NMR (200 MHz, CDCl3 BF3·OEt2) δ 32.0; FTIR
(film, cm−1) 3370, 1732, 1614; mp: 155−157 °C (acetone/petroleum
ether); Anal. Calcd for C31H33BN2O4 (508.25): C, 73.23; H, 6.54; N,
5.51. Found: C, 73.31; H, 6.49; N, 5.53. The chemical−physical data
are according to the literature.11
Methyl 2-Amino-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)-1H-indol-3-yl)propanoate (5). To a solution of 4
(2 g, 3.94 mmol) in THF (freshly distilled) (16 mL) was added 1 N
HCl (8 mL) at 0 °C. The mixture was stirred at 0 °C for 30 min and
then at room temperature for 2 h. The mixture was diluted with
CH2Cl2 (30 mL) and poured into a saturated solution of NaHCO3 (25
mL) at 0 °C. The phases were separated, and the aqueous phase was
extracted with further CH2Cl2 (10 × 20 mL). The combined organic
phases were dried over anhydrous Na2SO4, and the solvent was
evaporated under reduced pressure. The residue obtained was
triturated with n-hexane (2 × 15 mL), and then ether anhydrous
(20 mL) and pinacol (931 mg, 7.88 mmol) were added. The mixture
was stirred at room temperature for 12 h. The solvent was evaporated
under reduced pressure, and the residue obtained was purified by flash
chromatography (gradient from EtOAc to EtOAc/MeOH 97:3) to
obtained 1 g (2.91 mmol) of 5 as a white solid. Yield 74%. TLC
(EtOAc), Rf = 0.24 (UV, p-anisaldehyde); MS (ESI) 345 [M + 1]+; 1H
NMR (200 MHz, CDCl3) δ 1.40 (s, 12H), 1.80 (br s, 2H), 3.22 (dd, J1
= 14.0, J2 = 9.0 Hz, 1H), 3.63 (dd, J1 = 14.0, J2 = 5.0 Hz, 1H), 3.71 (s,
3H), 3.89 (dd, J1 = 9.0, J2 = 5.0 Hz, 1H), 7.06 (d, J = 2.0 Hz, 1H), 7.18
(d, J = 7.5 Hz, 1H), 7.43 (d, J = 7.5 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H),
8.47 (br s, 1H); 13C NMR (50 MHz, CDCl3) δ 24.8, 24.9, 31.5, 51.7,
55.6, 83.7, 113.2, 114.2, 121.1, 124.5, 128.8, 130.1, 136.3, 175.8
(carbon adjacent to boron was not observed); 11B NMR (64 MHz,
CDCl3 BF3·OEt2) δ 32.27; IR (nujol, cm−1) 3524, 1738; mp: 150−153
°C (CH2Cl2/n-hexane); Anal. Calcd for C18H25BN2O4 (344.19): C,
62.81; H, 7.32; N, 8.14. Found: C, 62.96; H, 7.28; N, 8.10.
An analytical sample of the intermediate imine 7 was purified by
flash chromatography (EtOAc) for the characterization. MS (ESI) 411
[M + 1]+; 1H NMR (200 MHz, CDCl3) δ 1.38 (s, 12H), 1.59 (s, 3H),
1.81 (s, 3H), 3.25(dd, J1 = 14.0, J2 = 9.5 Hz, 1H), 3.75 (s, 3H), 3.96
(dd, J1 = 14.0, J2 = 4.0 Hz, 1H), 4.13 (dd, J1 = 9.5, J2 = 4.0 Hz, 1H),
5.98 (d, J = 9.5 Hz, 1H), 6.98 (d, J = 2.0 Hz, 1H), 7.18 (t, J = 7.5 Hz,
1H), 7.45 (t, J = 7.5 Hz, 1H), 7.56 (d, J = 9.5 Hz, 1H), 7.69 (d, J = 7.5
Hz, 1H), 8.17 (br s, 1H); 13C NMR (50 MHz, CDCl3) δ 18.5, 24.6,
24.9, 26.6, 29.7, 51.9, 73.7, 83.7, 112.9, 114.2, 120.9, 125.0, 126.0,
129.0, 136.3, 147.6, 148.1, 162.1, 173.1 (carbon adjacent to boron was
not observed); IR (nujol, cm−1) 1735, 1655. The compound is too
unstable to obtain a good elemental analysis.
(1S,3S)-1-(2-Methylprop-1-enyl)-2,3,4,6-tetrahydro-1H-
azepino[5,4,3-cd]indol-2-ium-3-carboxylate (1a). A solution of
8a (35 mg, 0.12 mmol) in 3.8 mL of 4% KOH in MeOH−H2O (2:1)
was stirred for 45 min at room temperature. The solution was
concentrated to half volume and purified by flash chromatography
(CH2Cl2/MeOH/NH3 90:9:1) to give 26 mg (0.096 mmol) of 1a as a
white solid. Yield 81%. TLC (CH2Cl2:MeOH:NH4OH/75:25:1) Rf =
0.16 (UV, p-anisaldehyde, ninhydrin); MS (ESI) 271 [M + H]+; 269
1
[M − H]+; H NMR (200 MHz, CD3OD) δ 1.96 (s, 3H), 1.99 (s,
3H), 3.21 (ddd, J1 = 16.5, J2 = 12.0, J3 = 1.5 Hz, 1H), 3.85 (dd, J1 =
16.5, J2 = 3.5 Hz, 1H), 4.13 (dd, J1 = 12.0, J2 = 3.5 Hz, 1H), 5.57 (d, J2
= 10.0 Hz, 1H), 5.63 (d, J2 = 10.0 Hz, 1H), 6.85 (d, J = 8.0
Hz,1H),7.12 (t, J = 8.0 Hz,1H), 7.25 (s, 1H), 7.37 (d, J = 8.0 Hz, 1H);
13C NMR (50 MHz, CD3OD) δ 17.1, 24.6, 27.3, 59.9, 109.5, 111.3,
117.6, 120.8, 120.9, 122.8, 124.0, 127.4, 137.3, 141.6, 174.3. The
chemical−physical data are according to the literature.7h
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Tables 1−5 and copies of H NMR and 13C NMR spectra for
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: giovanni.piersanti@uniurb.it.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We would like to thank Prof. Gilberto Spadoni, University of
Urbino, for useful discussions.
cis-Methyl 1-(2-Methylprop-1-enyl)-2,3,4,6-tetrahydro-1H-
azepino[5,4,3-cd]indole-3-carboxylate (8a). To a solution of 5
(344 mg, 1 mmol) in DME (freshly distilled) (8 mL) were added 4 Å
molecular sieves (1 g) and 3-methylbut-2-enal (6) (105 μL, 1.1
mmol). The mixture was stirred at 30 °C for 4 h. The solution was
diluted with further DME (12 mL), and then CsF (456 mg, 3 mmol)
and [Rh(OH)cod]2 (46 mg, 0.1 mmol) were added. The mixture was
stirred at 85 °C for 16 h. The solvent was evaporated under reduced
pressure, and the residue obtained was purified by flash chromatog-
raphy (cyclohexane/EtOAc 7:3) to give 178 mg (0.63 mmol) of 8a as
yellowish solid. Yield 63%. TLC (cyclohexane/EtOAc, 7:3), Rf = 0.35
(UV, p-anisaldehyde); MS (ESI) 285 [M + 1]+; 1H NMR (200 MHz,
CDCl3) δ 1.85 (d, J = 1.0 Hz, 3H), 1.89 (d, J = 1.0 Hz, 3H), 2.68 (br s,
1H), 3.07 (ddd, J1 = 15.5, J2 = 12.0, J3 = 1.0 Hz, 1H), 3.56 (dd, J1 =
15.5, J2 = 2.5 Hz, 1H), 3.83 (s, 3H), 3.84 (dd, J1 = 12.0, J2 = 2.5 Hz,
1H), 4.90 (d, J = 9.0 Hz, 1H), 5.52 (d, J = 9.0 Hz, 1H), 6.87 (d, J = 7.5
Hz, 1H), 6.97 (s, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.21 (d, J = 7.5 Hz,
1H), 8.44 (br s, 1H); 13C NMR (50 MHz, CDCl3) δ 18.4, 25.8, 33.7,
52.4, 61. 9, 62.2, 109.4, 113.0, 117.8, 121.51, 121.53, 125.0, 127.4,
134.4, 137.0, 137.4, 174.6; IR (nujol, cm−1) 2923, 2853, 1726; mp:
133−134 °C (n-hexane/DCM); Anal. Calcd for C17H20N2O2
(284.15): C, 71.81; H, 7.09; N, 9.85. Found: C, 72.02; H, 7.16; N,
9.76. The chemical−physical data are according to the literature.7h
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