Practical and high stereoselective synthesis of 3-(arylmethylene) isoindolin-1-ones from 2-formylbenzoic acid

Article abstract of DOI:10.1016/j.tetlet.2012.08.040

Practical and high stereoselective synthesis of 3-(arylmethylene) isoindolin-1-ones is reported. The synthetic method involves the preparation of dimethyl isoindolin-1-one-3-yl-phosphonates by a 'one-pot' three-component reaction of 2-formylbenzoic acid with 4-methoxybenzylamine or aminoacetaldehyde dimethyl acetal and dimethyl phosphite under solvent and catalyst free-conditions, followed by a Horner reaction with several aryl aldehydes.

Full text of DOI:10.1016/j.tetlet.2012.08.040

Tetrahedron Letters 53 (2012) 5756–5758
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Tetrahedron Letters
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Practical and high stereoselective synthesis of
3-(arylmethylene)isoindolin-1-ones from 2-formylbenzoic acid
⇑
Miguel Angel Reyes-González, Angel Zamudio-Medina, Mario Ordóñez
Centro de Investigaciones Químicas - Universidad Autónoma del Estado de Morelos Av. Universidad 1001, 62209 Cuernavaca, Morelos, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones is reported. The syn-
thetic method involves the preparation of dimethyl isoindolin-1-one-3-yl-phosphonates by a ‘one-pot’
three-component reaction of 2-formylbenzoic acid with 4-methoxybenzylamine or aminoacetaldehyde
dimethyl acetal and dimethyl phosphite under solvent and catalyst free-conditions, followed by a Horner
reaction with several aryl aldehydes.
Received 25 July 2012
Accepted 9 August 2012
Available online 16 August 2012
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
One-pot three-component reaction
3-Methyleneisoindolin-1-ones
Horner reaction
Aminophosphonates
2-Formylbenzoic acid
Introduction
Due to the utility of substituted 3-methyleneisoindolin-1-ones
as key synthetic intermediates in conjunction with their biological
Substituted 3-methyleneisoindolin-1-ones type 1 are present in a
great variety of natural products and are also known to possess a
broad range of biological activities. For example, AKS 186 was found
to inhibit vasoconstriction induced by thromboxane A2 analog,1
whereas the derivative 2 has been claimed to exhibit local anesthetic
activity superior to that of procaine,2 and the compound 3 that pre-
sentedsedativeactivity.3 Additionally, the3-(arylmethylene)isoindo-
lin-1-ones are useful intermediates in the synthesis of aristolactams,4
lennoxamine,5 narceine imide,6 aristocularines,7 fumaridine,8 fuma-
ramidine,9 and in the synthesis of other heterocyclic compounds.10
activity, several synthetic protocols for their synthesis have been
developed in the last years, including the heteroannulation of o-
(1-alkynyl)benzamides induced by treatment with a base11 or a
palladium(II) catalyst, Pd-catalyzed heteroannulations involving
2-iodobenzamides and terminal alkynes,12 palladium(0)-catalyzed
three-component reaction of 2-bromoacetophenone and a variety
of primary amines under carbon monoxide pressure or titanium-
isocyanate complex and carbon monoxide,13 palladium-catalyzed
carbonylation-hydroamination reaction of 1-halo-2-alkynylben-
zene with amines,14 ‘one-pot’ regioselective elimination cycliza-
tion-Suzuki approach15 or Sonogashira reaction of 2-(2,2-
dihalovinyl)-benzamides,16 reaction of phthalic anhydride with
phenylacetic acid and sodium acetate and subsequent treatment
with the appropriate amine,17 CuI/L-proline catalyzed coupling of
2-bromobenzamides and terminal alkynes,18 the Heck–Suzuki–
Miyaura domino reactions involving ynamides,19 iodocyclization
of (E)-2-alk-1-enyl-N-benzylbenzamides,20 reaction of isoindolin-
1-ones with aldehydes,21 photodecarboxylative benzylations of
phthalimide,22 and the Horner condensation of 3-(diphenyl-phos-
phinoyl)isoindolin-1-ones with aldehydes.23 However, in spite of
their potential utility, these procedures typically suffer from one
or more disadvantages such as the use of expensive reagents or
poor regioselectivity in the cases of unsymmetrical substrates,
therefore is desirable to develop a more efficient, simple, and
milder protocol.
O
O
N
N
R'
R''
R
OH
1
AKS 186
O
O
Me
Me
NEt2
N
F
N
O
N
N
AcO
Me
During our program aimed at the convenient synthesis of cyclic
a
-aminophosphonates,24 herein, we report a new synthetic strat-
2
3
egy for the high stereoselective synthesis of 3-(arylmethylene)-iso-
indolin-1-ones N-substituted 7 and 8 by the Horner reaction of
⇑
Corresponding author. Tel./fax: +52 777 329 7997
E-mail address: palacios@uaem.mx (M. Ordóñez).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.040

M. A. Reyes-González et al. / Tetrahedron Letters 53 (2012) 5756–5758
5757
Table 2
several aromatic aldehydes and dimethyl isoindolin-1-one-3-yl-
Synthesis of 3-arylmethyleneisoindolin-1-ones 7, 8
phosphonates easily available from an ‘one-pot’ three-component
reaction of 2-formylbenzoic acid with the appropriate amines
and dimethyl.
O
N
O
1. n-BuLi/THF
N
R
R
-78°C,1h
2. ArCHO
Results and discussion
P(OMe)2
O
Ar
7a-f; R = PMB
8a-d; R = CH2CH(OMe)2
5; R = PMB
For the synthesis of the target compounds 7 and 8 initially we
decided to explore the use of 2-formylbenzoic acid 4 as starting
material taking into account its recent application in the synthesis
of N-substituted isoindolin-1-ones reported by us.25,26 Thus, the
‘one-pot’ three-component reaction of 2-formylbenzoic acid 4 with
4-methoxybenzylamine and dimethyl phosphite under microwave
irradiation (55 °C/180 W, 10 min.) and solvent free-conditions,
afforded the corresponding dimethyl 2-(4-methoxybenzyl)isoindo-
lin-1-one-3-yl-phosphonate 5 in 30% yield (Table 1, entry 1).
In order to establish the optimal conditions, the reaction was
carried out using methanol as solvent and reacted at different tem-
peratures and times, found that 55 °C/180 W, 10 min. were the
best conditions, obtaining phosphonate 5 in 71% yield (Table 1,
entry 2).27
6; R = CH2CH(OMe)2
Entry
Ar
Yield (%)
E:Z
90:10
1
2
3
4
5
6
7
8
9
10
C6H5
4-ClC6H4
2-BrC6H4
98
97
91
85
75
91
95
87
82
86
83:17
75:25
91:09
63:37
89:11
85:15
87:13
>98:02
92:08
4-MeOC6H4
2-Br,5-MeOC6H3
3,4-(MeO)2C6H3
C6H5
4-ClC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
Although this synthetic procedure proved to be a suitable meth-
odology to obtain the phosphonate 5, the low yield prompted us to
explore a new method for its preparation in a high yield manner.
With this purpose in mind, and looking for alternative protocols
under mild and environmentally friendly reaction conditions, we
decided to explore the ‘one-pot’ three-component reaction of 2-
formylbenzoic acid 4 with 4-methoxybenzylamine and dimethyl
phosphite at 50 °C under solvent and catalyst free-conditions,
obtaining the expected isoindolin-1-one-3-phosphonate 5 in 87%
yield (Table 1, entry 3).28 In a similar way, the ‘one-pot’ three-com-
ponent reaction of 2-formylbenzoic acid 4 with aminoacetalde-
hyde dimethyl acetal and dimethyl phosphite under microwave
irradiation gave the corresponding isoindolin-1-one-3-phospho-
nate 6 in 19 and 50% yield (Table 1, entries 4 and 5). Finally, the
same reaction at 50 °C under solvent and catalyst free-conditions
The E-form predominantly was assigned from their 1H NMR spec-
tra with the help of NOE experiment and confirmed by analogy
with the results reported in the literature.11b,14
After optimization of experimental conditions of the Horner
reaction of isoindolin-1-one-3-phosphonate 5 with benzaldehyde,
we extended this protocol with other aromatic aldehydes, obtain-
ing the corresponding 3-(arylmethylene)isoindolin-1-ones 7b–f in
excellent yields and with a selectivity E:Z from 63:37 to 91:09 (Ta-
ble 2, entries 2–6).
Identically, the Horner reaction of isoindolin-1-one-3-phospho-
nate 6 with several aromatic aldehydes using n-BuLi as base in THF
a À78 °C gave the corresponding 3-(arylmethylene)-isoindolin-1-
ones 8a–d in 82–95% yield and with an excellent selectivity E:Z
85:15 to >98:02 (Table 2, entries 7–10).
In summary, we have reported an efficient and high stereoselec-
tive access to (E)-3-(arylmethylene)isoindolin-1-ones by using the
Horner reaction of aromatic aldehydes and dimethyl isoindolin-1-
one-3-yl-phosphonates easily available in large scale in only one
step under solvent and catalyst free-conditions. This process,
which further expands the synthetic utility of (E)-3-(arylmethyl-
ene)isoindolin-1-ones, will be applied to the preparation of natural
and/or biologically active compounds.
provided the isoindolin-1-one-3-phosphonate
6 in 91% yield
(Table 1, entry 6).29
With the isoindolin-1-one-3-phosphonates 5 and 6 in hand, in
the next step we turned our attention to the Horner reaction with
several aromatic aldehydes to obtain the desired 3-(aryl-methy-
lene)isoindolin-1-ones 7a–f and 8a–d. In this context, the treat-
ment of the isoindolin-1-one-3-phosphonate 5 with n-BuLi in
THF a À78 °C followed by the addition of benzaldehyde afforded
the corresponding 3-(benzylidene)isoindolin-1-one 7a in quantita-
tive yield and with a selectivity E:Z of 90:10 (Table 2, entry 1).30
Acknowledgments
The authors thank the CONACYT of Mexico, for financial support
via project (62271). We thank to V. Labastida-Galván and S. Lagun-
as-Rivera for their technical assistance. One of us, MGX also thank
the CONACYT for Graduate Scholarships.
Table 1
Synthesis of isoindolin-1-one-3-phosphonates 5, 6
O
CO2H
+
H2N R
N
R
References and notes
CHO
P(OMe)2
1. (a) Kato, Y.; Takemoto, M.; Achiwa, K. Chem. Pharm. Bull. 1993, 41, 2003–2006;
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Tetrahedron Lett. 1998, 39, 2285–2288.
O
4
O
H P(OMe)2
5; R = PMB
6; R = CH2CH(OMe)2
2. Laboratori Baldacci, S.p.A. JP Patent 59,046,268, 1984; Chem. Abstr. 1984, 101,
54922.
Entry
R
Conditions
Yield (%)
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769.
1
2
3
4
5
6
4-MeOC6H4CH2
4-MeOC6H4CH2
4-MeOC6H4CH2
(MeO)2CHCH2
(MeO)2CHCH2
(MeO)2CHCH2
55 °C, 10 min.a
MeOH, 55 °C, 10 min.a
50 °C, 5 h.b
30
78
87
19
50
91
55 °C, 10 min.a
MeOH, 55 °C, 10 min.a
50 °C, 5 h.b
a
The reaction was carried out at 180 watts.
The reaction was carried under conventional heating.
b

5758
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Schmid, B.; Knochel, P. Tetrahedron 2003, 59, 1571–1587.
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2984–2989.
29. Dimethyl
2-(2,2-dimethoxyethyl)isoindolin-1-one-3-ylphosphonate
6.
Aminoacetaldehyde dimethyl acetal (1.68 g, 16 mmol) was added to 2-
formylbenzoic acid (2.0 g, 13.3 mmol) and the mixture was stirred at room
temperature for 15 min prior to the addition of dimethyl phosphite (1.76 g,
16 mmol). The reaction mixture was stirred at 50 °C for 5 h, and the crude
product was purified by flash column chromatography (AcOEt/hexanes = 3:1),
obtaining (3.94 g, 91%) as a white solid; mp 63–65 °C. 1H NMR (400 MHz,
CDCl3): d 3.37 (s, 3H, CH3O), 3.42 (s, 3H, CH3O), 3.52 (d, J = 11.2 Hz, 3H,
(CH3O)2P), 3.68 (dd, J = 6.4, 6.8 Hz, 1H, CH2N), 3.78 (d, J = 10.8 Hz, 3H,
(CH3O)2P), 4.32 (dd, J = 3.6, 3.6 Hz, 1H, NCH2), 4.55 (dd, J = 6.8, 3.6 Hz, 1H,
CH(OCH3)2), 5.24 (d, J = 13.2 Hz, 1H, CHP(OMe)2), 7.51–7.54 (m, 1H, Harom),
7.58–7.62 (m, 1H, Harom), 7.77–7.79 (m, 1H, Harom), 7.88–7.90 (m, 1H, Harom).
13C NMR (100 MHz, CDCl3): d 42.8, 53.7 (d, J = 7.6 Hz, (CH3O)2P), 53.8 (d,
J = 7.6 Hz, (CH3O)2P), 54.1, 54.9, 57.9 (d, J = 153.2 Hz, CHP(OMe)2), 102.9, 124.0,
124.6, 128.8, 131.9, 139.0, 139.1, 169.1 (C@O). 31P NMR (81 MHz, CDCl3): d
21.71. HRMS [CI+]: Anal. Calcd for C14H21NO6P: 330.1028. Found: 330.1123.
30. Typical procedure for the synthesis of 3-(arylmethylene)-isoindolin-1-ones
7a–f and 8a–d. A solution of n-BuLi (1.0 equiv) was added dropwise to a stirred
solution of the isoindolin-1-one-3-yl-phosphonates 5 or 6 (1.0 equiv) in THF
(15 mL) at À78 °C under nitrogen. The solution was stirred for 15 min at this
temperature and after this time the corresponding aryl aldehyde (1.0 equiv)
was added. The reaction mixture was stirred at À78 °C for 15 min and then
warmed to room temperature over a period of 1 h. The reaction mixture was
quenched by the addition of saturated solution of NH4Cl and extracted with
AcOEt (2 Â 20 mL). The organic extracts were dried over Na2SO4, filtered and
evaporated in vacuo. The crude product was analyzed by 1H NMR and then
purified by flash column chromatography (AcOEt/hexanes = 2:1), obtaining the
corresponding 3-(arylmethylene)isoindolin-1-ones. Spectroscopic data for
7a,11b,14 7c,11b 7d,4b and 8d5a were identical with those reported in the
literature. 7b; Yield: 303 mg, 97% (E/Z isomers ratio 83:17) as a white solid; mp
123–126 °C. (E)-isomer; 1H NMR (400 MHz, CDCl3) d: 3.77 (s, 3H, CH3O), 5.03
(s, 2H, CH2N), 6.38 (s, 1H, CH), 6.84–6.87 (m, 2H, Harom), 7.21–7.36 (m, 8H,
17. Botero Cid, H. M.; Tränkle, C.; Baumann, K.; Pick, R.; Mies-Klomfass, E.;
Kostenis, E.; Mohr, K.; Holzgrabe, U. J. Med. Chem. 2000, 43, 2155–2164.
18. (a) Li, L.; Wang, M.; Zhang, X.; Jiang, Y.; Ma, D. Org. Lett. 2009, 11, 1309–1312;
(b) Hellal, M.; Cuny, G. D. Tetrahedron Lett. 2011, 52, 5508–5511.
19. (a) Couty, S.; Liégault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511–2514; (b)
Refs. 5b and 5c.
20. Cherry, K.; Duchêne, A.; Thibonnet, J.; Parrain, J.-L.; Anselmi, E.; Abarbri, M.
Synthesis 2009, 257–270.
H
arom), 7.42–7.46 (m, 1H, Harom), 7.88–7.90 (m, 1H, Harom). 13C NMR (100 MHz,
21. (a) Couture, A.; Deniau, E.; Grandclaudon, P.; Hoarau, C.; Rys, V. Tetrahedron
Lett. 2002, 43, 2207–2210; (b) Refs. 4c and 9.
CDCl3) d: 42.8, 55.4, 110.1, 114.3, 123.2, 123.6, 128.5, 128.9, 129.6 (2C), 130.3,
131.0, 131.9, 133.7, 133.8, 135.0, 136.6, 159.0, 167.0 (C@O). HRMS [CI+]: Anal.
Calcd for C23H19NO2Cl: 376.1026. Found: 376.1119. 7e; Yield: 180 mg, 75% (E/Z
isomers ratio 63:37) as a yellow solid; mp 150–153 °C. (E)-isomer; 1H NMR
(400 MHz, CDCl3 d: 3.73 (s, 3H, CH3O), 3.76 (s, 3H, CH3O), 5.06 (s, 2H, CH2N),
6.33 (s, 1H, CH), 6.49–6.52 (m, 1H, Harom), 6.61–6.63 (m, 1H, Harom), 6.84–6.86
(m, 2H, Harom), 6.99–7.0 (m, 1H, Harom), 7.20–7.31 (m, 4H, Harom), 7.49–7.52 (m,
1H, Harom), 7.88–7.92 (m, 1H, Harom). 13C NMR (100 MHz, CDCl3) d: 42.9, 55.4,
55.7, 110.8, 113.8, 114.3, 115.8, 119.8, 123.3, 123.6, 127.6, 128.7, 129.6, 130.5,
131.9, 133.6, 135.0, 136.4, 136.7, 158.8, 159.1, 166.8. HRMS [CI+]: Anal. Calcd
for C24H21NO3Br: 450.0627. Found: 450.0719. 7f. Yield: 300 mg, 91% (E/Z
isomers ratio 89:11) as a white solid; mp 181–185 °C. (E)-isomer; 1H NMR
(400 MHz, CDCl3) d: 3.77 (s, 3H, CH3O), 3.83 (s, 3H, CH3O), 3.92 (s, 3H, CH3O),
5.04 (s, 2H, CH2N), 6.46 (s, 1H, CH), 6.84–6.92 (m, 5H, Harom), 7.23–7.45 (m, 5H,
22. (a) Belluau, V.; Noeureuil, P.; Ratzke, E.; Skvortsov, A.; Gallagher, S.; Motti, C.
A.; Oelgemöller, M. Tetrahedron Lett. 2010, 51, 4738–4741; (b) Griesbeck, A. G.;
Warzecha, K.-D.; Neudörfl, J. M.; Görner, H. Synlett 2004, 2347–2350.
23. (a) Couture, A.; Deniau, E.; Grandclaudon, P. Tetrahedron 1997, 53, 10313–
10330; (b) Refs. 4b, 4c, 5a, 7, 8
24. (a) Arizpe, A.; Sayago, F. J.; Jiménez, A. I.; Ordóñez, M.; Cativiela, C. Eur. J. Org.
Chem. 2011, 6732–6738; (b) Arizpe, A.; Sayago, F. J.; Jiménez, A. I.; Ordóñez, M.;
Cativiela, C. Eur. J. Org. Chem. 2011, 3074–3081.
25. Ordóñez, M.; Tibhe, G. D.; Zamudio-Medina, A.; Viveros-Ceballos, J. L. Synthesis
2012, 44, 569–574.
26. Viveros-Ceballos, J. L.; Cativiela, C.; Ordoñez, M. Tetrahedron: Asymmetry 2011,
22, 1479–1484.
27. Synthesis of dimethyl 2-(4-methoxybenzyl)isoindolin-1-one-3-yl-phosphonate
5 under microwave irradiation: 4-Methoxybenzyl-amine (1.0 g, 7.3 mmol) was
added to 2-formylbenzoic acid (1.0 g, 6.7 mmol) in methanol 10 mL, was
irradiated under CEM microwave at 55 °C and 180 W for 5 min. After this time,
dimethyl phosphite (879 mg, 8 mmol) was added and the reaction mixture
was irradiated again at 55 °C, 180 W for 5 min. The crude product was purified
by flash column chromatography (AcOEt/hexanes = 1:1), obtaining (1.9 g, 78%).
28. Dimethyl 2-(4-methoxybenzyl)isoindolin-1-one-3-yl-phosphonate 5. 4-
Methoxybenzylamine (910 mg, 6.6 mmol) was added to 2–formylbenzoic
acid (1.0 g, 6.7 mmol) and the mixture was stirred at room temperature for
15 min prior to the addition of dimethyl phosphite (879 mg, 8 mmol). The
reaction mixture was stirred at 50 °C for 5 h, and the crude product was
purified by flash column chromatography (AcOEt/hexanes = 1:1), obtaining
(2.1 g, 87%) as a white solid; mp 113–116 °C. 1H NMR (400 MHz, CDCl3): d 3.58
(d, J = 10.8 Hz, 3H, (CH3O)2P), 3.75 (d, J = 10.8 Hz, 3H, (CH3O)2P), 3.77 (s, 3H,
CH3O), 4.48 (system AB, J = 14.8 Hz, 1H, CH2N), 4.68 (d, J = 13.6 Hz, 1H,
CHP(OCH3)2), 5.51 (system AB, J = 14.8 Hz, 1H, CH2N), 6.80–6.84 (m, 2H, Harom),
7.23–7.26 (m, 2H, Harom), 7.50–7.58 (m, 2H, Harom), 7.67–7.69 (m, 1H, Harom),
7.90–7.92 (m, 1H, Harom). 13C NMR (100 MHz, CDCl3): d 44.6, 53.8 (d, J = 7.6 Hz,
(CH3O)2P), 55.1 (d, J = 7.6 Hz, (CH3O)2P), 55.2, 55.7 (d, J = 155.0 Hz,
CHP(OMe)2), 114.2, 124.2, 124.5, 129.1, 129.9, 130.5, 131.8, 132.1, 138.5,
159.3, 168. (C@O). 31P NMR (81 MHz, CDCl3): d 21.45. HRMS [CI+]: Anal. Calcd
for C18H21NO5P: 362.1079. Found: 362.1141.
H
arom), 7.88–7.90 (m, 1H, Harom). 13C NMR (100 MHz, CDCl3) d: 42.8, 55.4, 56.1
(2C), 111.3, 111.6, 112.7, 114.2, 122.3, 123.4, 123.5, 127.7, 128.5, 129.2, 129.3,
130.3, 131.6, 135.3, 135.8, 148.9, 149.0, 159.0, 166.8 (C@O). HRMS [CI+]: Anal.
Calcd for C25H24NO4: 402.1627. Found: 402.1706. 8a; Yield: 267 mg, 95% (E/Z
isomers ratio 85:15) as a green oil. (E)-isomer; 1H NMR (400 MHz, CDCl3) d:
3.45 (s, 6H, CH3O), 4.03 (d, J = 5.2 Hz, 1H, CH2N), 4.72 (t, J = 5.2 Hz, 1H,
CH(OCH3)2), 6.74 (s, 1H, CH), 7.28–7.45 (m, 8H, Harom), 7.83–7.87 (m, 1H,
H
arom). 13C NMR (100 MHz, CDCl3) d: 42.3, 54.7, 102.6, 111.4, 123.4, 127.8,
127.9, 128.9 (2C), 129.3, 129.8, 131.7, 134.1, 135.5, 136.8, 167.0 (C@O). HRMS
[CI+]: Anal. Calcd for C19H20NO3: 310.1365. Found: 310.1448. 8b; Yield:
272 mg, 87% (E/Z isomers ratio 87:13) as a green oil. (E)-isomer; 1H NMR
(400 MHz, CDCl3) d: 3.45 (s, 6H, CH3O), 4.0 (d, J = 5.2 Hz, 2H, CH2N), 4.69 (t,
J = 5.2 Hz, 1H, CH(OCH3)2), 6.66 (s, 1H, CH), 7.27–7.45 (m, 6H, Harom), 7.70–7.75
(m, 1H, Harom), 7.83–7.87 (m, 1H, Harom). 13C NMR (100 MHz, CDCl3) d: 42.3,
54.8, 102.7, 109.9, 123.2, 123.5, 129.1, 129.6, 130.2, 131.1, 131.8, 133.9, 134.0,
135.2, 137.2, 167.0 (C@O). HRMS [CI+]: Anal. Calcd for C19H19NO3Cl: 344.0975.
Found: 344.1060. 8c; Yield: 252 mg, 82% (E/Z isomers ratio >98:2) as a green
oil. (E)-isomer; 1H NMR (400 MHz, CDCl3) d: 3.44 (s, 6H, CH3O), 3.87 (s, 3H,
CH3O), 4.03 (d, J = 5.2 Hz, 2H, CH2N), 4.71 (t, J = 5.2 Hz, 1H, CH(OCH3)2), 6.69 (s,
1H, CH), 6.95–6.98 (m, 2H, Harom), 7.28–7.42 (m, 5H, Harom), 7.83–7.86 (m, 1H,
H
arom). 13C NMR (100 MHz, CDCl3) d: 42.3, 54.7, 55.5, 102.7, 111.4, 114.3, 123.2,
123.3, 127.7, 129.1, 130.2, 131.0, 131.2, 131.7, 135.5, 136.2, 159.6 (C@O).
HRMS [CI+]: Anal. Calcd for C20H22NO4: 340.1471. Found: 340.1561.