Electrophilic Cyclization of o -Anisole- and o -Thioanisole-Substituted Ynamides: Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes

Article abstract of DOI:10.1055/s-0033-1338481

A facile synthesis of 3-substituted 2-amidobenzofurans and 2-amidobenzothiophenes via electrophilic cyclization reaction of o-anisole- and o-thioanisole-substituted ynamides with I₂, NBS and NCS was developed. The products 3-iodo-2-amidobenzofurans were further transferred into 3-aryl-, 3-alkynyl, and 3-vinyl-2-amidobenzofurans via Pd-catalyzed reactions such as Suzuki-Miyaura and Sonogashira cross-coupling reactions and the Heck reaction. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1338481

PAPER
▌1975
paper
Electrophilic Cyclization of o-Anisole- and o-Thioanisole-Substituted Ynamides:
Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes
Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes
Yulong Kong, Lian Yu, Lingzi Fu, Jian Cao,* Guoqiao Lai, Yuming Cui, Ziqiang Hu, Guanhai Wang
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University,
Wenyi Road 222, Hangzhou 310012, P. R. of China
Fax +86(571)28865135; E-mail: caojian@hznu.edu.cn
Received: 25.03.2013; Accepted after revision: 24.04.2013
developed a carbocation-induced electrophilic cyclization
Abstract: A facile synthesis of 3-substituted 2-amidobenzofurans
reaction of o-anisole-substituted ynamides for the synthe-
and 2-amidobenzothiophenes via electrophilic cyclization reaction
sis of 3-alkyl- and 3-allenyl-2-amidobenzofurans.13 In
continuation of the study on electrophilic cyclization reac-
of o-anisole- and o-thioanisole-substituted ynamides with I2, NBS
and NCS was developed. The products 3-iodo-2-amidobenzofurans
were further transferred into 3-aryl-, 3-alkynyl, and 3-vinyl-2-ami- tion of ynamides, we wish to report herein a halocycliza-
dobenzofurans via Pd-catalyzed reactions such as Suzuki–Miyaura
and Sonogashira cross-coupling reactions and the Heck reaction.
tion reaction of o-anisole- and o-thioanisole-substituted
ynamides for the synthesis of 3-halogenated-2-amidoben-
Key words: 2-amidobenzofurans, 2-amidobenzothiophenes, elec-
trophilic cyclization, ynamide, cross-coupling reaction
zofurans and -benzothiophenes, which could be readily
transferred into 3-aryl-, 3-vinyl, and 3-alkynyl-2-amido-
benzofurans and -2-amidobenzothiophenes via Pd-cata-
lyzed cross-coupling reactions (Scheme 1). This two-step
Benzofuran1 and benzothiophene2 are the fundamental protocol may be well complementary to our previous car-
motifs in both synthetic and naturally occurring com- bocation-induced electrophilic cyclization strategy.
pounds that exert a wide range of pharmacological activi-
ties. Thus, various methods have been established for the
The o-anisole- and o-thioanisole-substituted ynamides are
readily prepared via the Cu-catalyzed cross-coupling re-
synthesis of these heterocycles, including electrophilic
actions of alkynyl bromides and amides.9c We initially ex-
cyclization chemistry.3 As their functionalized deriva-
amined the reaction of o-anisole-substituted ynamide 1a
tives, 2-amidobenzofurans4 and 2-amidobenzothio-
(0.5 mmol in 4 mL of CH2Cl2) with I2 (1.5 equiv). To our
phenes,5 attract considerable interest for biological and
delight, 1a reacted in less than one hour at room tempera-
ture to afford 3-iodo-2-amidobenzofuran 2a in excellent
physiological effects. While several methods have been
reported for the synthesis of these derivatives,6,7 they are
yield (Table 1, entry 1). Other common solvents such as
generally limited with respect to the availability of start-
THF, MeCN, and toluene were effective as well, although
ing materials and the types and locations of substituents in
lower yields were obtained (entries 2–4). Besides I2, yn-
amide 1a reacted smoothly with the mild halogenated
products.
In recent years, ynamides have emerged as important syn- reagents N-bromosuccinimide (NBS) and N-chloro-
thons in modern organic synthesis.8 The ready succinimide (NCS) to form 3-bromo-2-amidobenzofuran
availability9 and high reactivity10 of these specially func- 2b (entry 6) and 3-chloro-2-amidobenzofuran 2c (entry
tionalized alkynes makes them ideal as starting materials 8), respectively. Other electrophiles such as NIS, and
for the synthesis of various heterocyclic compounds. Re- CuBr2 were less effective (entries 5, 7) and corresponding
cently, 2-amidobenzofurans were constructed via transi- halocyclization with CuCl2 and Selectfluor was unsuc-
tion metal-catalyzed reactions of ynamides by the groups cessful (entries 9, 10).
of Hsung11 and Skrydstrup,12 respectively. Our group also
EWG
Pd-catalyzed
R2
X
cross-
N
X+
coupling
R
EWG
R1
EWG
R1
N
N
Y
Y
YMe
R2 = aryl, vinyl, alkynyl
X = I, Br, Cl
Y = O, S
Scheme 1 Two-step synthesis of 2-amidobenzofurans and benzothiophenes
SYNTHESIS 2013, 45, 1975–1982
Advanced online publication: 15.05.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1338481; Art ID: SS-2013-H0230-OP
© Georg Thieme Verlag Stuttgart · New York

1976
Y. Kong et al.
PAPER
Table 2 Synthesis of 2-Amidobenzofurans 2a (continued)
Entry Ynamide Electro- Yield (%) of product
Table 1 Effect of Reaction Conditions on the Cyclization Reactiona
Ts
X
N
phile
X+
Ts
Bn
N
solvent
5
1b
1b
NBS
NCS
2e, X = Br, 74
2f, X =Cl, 87
O
Bn
6b
OMe
2a, X = I
2b, X = Br
2c, X = Cl
1a
Ts
N
I
Ph
Entry
Electrophile Solvent
Yield (%) of product
Ts
N
N
N
7
I2
O
1
I2
CH2Cl2
toluene
THF
2a, 97
2a, 85
2a, 50
2a, 17
2a, 48
2b, 79
2b, 70
2c, 65
0
Ph
OMe
OMe
OMe
OMe
OMe
2g, 88
2
I2
1c
1d
1e
1f
3
I2
Ms
N
I
4
I2
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Bn
Ms
Bn
8
I2
5
NIS
NBS
CuBr2
NCS
CuCl2
selectfluor
O
6
2h, 77
7
Boc
N
I
8
Bn
Boc
Bn
9
9
I2
O
10
0
2i, 74
a Unless otherwise specified, the reaction was carried out using 1 (0.5
mmol) and electrophile (0.75 mmol) in CH2Cl2 (4 mL) at r.t.
Ts
N
Br
Ts
N
10
11
NBS
O
The scope of ynamides 1 was further investigated. As
shown in Table 2, the reactions were successful for sul-
fonamides (Table 2, entries 1, 7, 8, 10, 11), oxazolidinone
(entry 4) and acyclic carbamate (entry 9), and substituent
on the benzene ring did not affect the yield significantly
(entries 12, 13).
2j, 55
Ts
N
I
Ts
N
I2
O
Table 2 Synthesis of 2-Amidobenzofurans 2a
2k, 57
Entry Ynamide
Electro- Yield (%) of product
phile
1g
O
O
I
O
Br
N
Ts
N
O
N
X
Br
12
13
Ph I2
O
Bn
Ts
Ph
N
1
I2
OMe
O
O
Bn
2l, 77
OMe
1h
2a, X = I, 97
1a
1a
O
I
O
2
3
NBS
NCS
2b, X = Br, 79
2c, X = Cl, 65
N
O
N
1a
I2
Ph
O
O
Ph
O
X
O
OMe
2m, 83
N
O
1i
N
a Unless otherwise specified, the reaction was carried out using 1 (0.5
mmol) and electrophile (0.75 mmol) in CH2Cl2 (4 mL) at r.t.
b NCS used: 1.5 mmol.
4
Ph
I2
O
Ph
OMe
2d, X = I, 92
1b
Synthesis 2013, 45, 1975–1982
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes
1977
This halocyclization strategy was extended to the synthe-
sis of 2-amidobenzothiophenes. As expected, o-thio-
anisole-substituted ynamide 3a reacted smoothly with I2
to form 2-amido-3-iodobenzothiophene 4a in a 90% yield
(Table 3, entry 1). Bromocyclization and chlorocycliza-
tion with NBS and NCS afforded the 3-bromo-2-amido-
benzothiophene 4b (entry 2) and 3-chloro-2-
amidobenzothiophene 4c (entry 3), respectively. Besides
N-benzylsulfonamide 3a, N-phenylsulfonamide 3b and
oxazolidinone 3c also gave 3-halo-2-amidobenzothio-
phenes 4d (entry 4) and 4e (entry 5) in good yields.
Ts
X+
N
X
K2CO3
CH2Cl2
Bn
N
Ph
Bn
Ts
5a
X+ = I2
6a, X = I, 64%
X+ = NBS 6b, X = Br, 69%
O
Ts
I2
N
K2CO3
CH2Cl2
I
O
Bn
Ph
N
Bn
Ts
5b
6c, 39%
Table 3 Synthesis of 2-Amidobenzothiophenes 4a
Scheme 2 Synthesis of amidonaphthalenes and amidobenzopyrans
Entry
Ynamide
Electrophile Yield (%) of product
Ts
N
EWG
X
X
Bn
N
Ts
R
EWG
R
X+
N
1
I2
N
S
Bn
Y
SMe
2 or 4
YMe
1 or 3
4a, X = I, 90
3a
3a
X+
2
3
NBS
NCS
4b, X = Br, 91
4c, X = Cl, 75
X
3a
X
EWG
Ts
N
•
EWG
N
Br
N
R
Y
R
Ph
Ts
YMe
A
Me
B
N
4
5
NBS
NBS
S
Ph
SMe
Scheme 3 Proposed reaction mechanism
4d, 63
3b
O
O
The 3-iodo-2-amidobenzofurans and -benzothiophenes
obtained by this approach should be very useful for the
synthesis of 3-functionalized 2-amidobenzofurans and 2-
amidobenzothiophenes. For example, 3-iodo-2-amido-
benzofurans 2d and 2h can be further transferred into 3-
aryl-, 3-alkynyl-, and 3-vinyl-2-amidobenzofurans 7a, 7b,
and 7c via Pd-catalyzed reactions such as Suzuki–Miyaura
and Sonogashira cross-coupling reactions, and the Heck
reaction (Scheme 4).
Br
O
N
O
N
Ph
S
Ph
SMe
4e, 88
3c
a Unless otherwise specified, the reaction was carried out using 3 (0.5
mmol) and electrophile (0.75 mmol) in CH2Cl2 (4 mL) at r.t.
In conclusion, we have described a novel synthesis of 2-
amidobenzofurans and 2-amidobenzothiophenes via elec-
trophilic cyclization reaction of o-anisole- and o-thioan-
isole-substituted ynamides with I2, NBS, and NCS. 1-
Amidonaphthalenes and 1-amidobenzopyrans were also
constructed by this strategy from ynamides via the forma-
tion of a C–C bond. The 3-iodo-2-amidobenzofurans were
further transferred into 3-aryl-, 3-alkynyl- and 3-vinyl-2-
amidobenzofurans via Pd-catalyzed Suzuki–Miyaura and
Sonogashira cross-coupling reactions, and the Heck reac-
tion. This two-step strategy is well complementary to our
previous synthesis of 2-amidobenzofurans via carboca-
tion-induced electrophilic cyclization reaction.
This approach is not limited to the construction of hetero-
cycles. When an aryl group acts as a nucleophile, carbo-
cyclic system can also be obtained via the formation of a
C–C bond.14 As shown in Scheme 2, in the presence of
K2CO3, N-tosylenynamine 5a reacted with electrophiles
smoothly to afford 2-halo-1-amidonaphthalenes 6a and
6b. 1-Amidobenzopyran 6c could also be constructed
from ynamide 5b, although in lower yield.
A possible mechanism is given in Scheme 3. Electrophilic
addition of the electrophile with o-anisyl/o-thioanisyl yn-
amide 1/3 gives the intermediate keteniminium ions A.
Subsequent cyclization occurs to afford O/S-methylben-
zofuran/benzothiophene B, which is demethylated by
nucleophile to produce 2-amidobenzofuran/2-amidoben-
zothiophene 2/4.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1975–1982

1978
Y. Kong et al.
PAPER
13C NMR (100 MHz, CDCl3): δ = 144.6, 140.7, 134.8, 134.5, 131.8,
129.7, 128.9, 128.5, 128.3, 128.0, 127.8, 124.5, 124.3, 121.3, 88.8,
69.1, 55.9, 21.7, 15.3.
HRMS (ESI): m/z calcd for C23H22NO2S2 (M + H)+: 408.1086;
found: 408.1091.
I
O
Ph
O
Pd(OAc)2
Na2CO3
+ NaBPh4
N
N
DMF–H2O
100 °C
O
O
Ph
Ph
2d
7a, 92%
4-Methyl-N-{2-[2-(methylthio)phenyl]ethynyl}-N-phenylben-
zenesulfonamide (3b)
Ph
Yield: 1.637 g (52%); brown oil.
PdCl2(PPh3)2
CuI
O
Ph
IR (neat): 2921, 2233, 1593, 1490, 1370, 1169, 688 cm–1.
2d
+
Et3N, THF
r.t.
1H NMR (400 MHz, CDCl3): δ = 7.69–7.71 (2 H, d, J = 8.0 Hz),
7.24–7.42 (9 H, m), 7.04–7.15 (2 H, m), 2.45 (3 H, s), 2.42 (3 H, s).
N
O
Ph
7b, 99%
13C NMR (100 MHz, CDCl3): δ = 145.0, 141.7, 138.9, 133.1, 132.4,
129.6, 129.1, 128.6, 128.4, 128.2, 126.3, 124.35, 124.32, 120.9,
88.9, 68.3, 21.7, 15.2.
CO2Me
I
HRMS (ESI): m/z calcd for C22H19NO2S2 + Na (M + Na)+:
416.0749; found: 416.0762.
Pd(OAc)2
Ms
Bn
Ms
N
Na2CO3
+
CO2Me
N
n-Bu4NCl, DMF
O
O
Bn
3-{2-[2-(Methylthio)phenyl]ethynyl}-4-phenyloxazolidin-2-one
80 °C
2h
7c, 48%
(3c)
Yield: 1.111 g (45%); brown oil.
Scheme 4 Synthesis of 3-aryl-, 3-vinyl-, and 3-alkynyl-2-amidoben-
IR (neat): 2920, 2246, 1765, 1395, 1193, 1062, 746 cm–1.
zofurans
1H NMR (400 MHz, CDCl3): δ = 7.35–7.42 (5 H, m), 7.15–7.22 (2
H, m), 6.94–7.04 (2 H, m), 5.12 (1 H, dd, J = 7.2 Hz), 4.72 (1 H, dd,
J = 7.2 Hz), 4.24 (1 H, dd, J = 7.2 Hz), 2.27 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 155.4, 141.3, 136.2, 132.1, 129.4,
129.3, 128.6, 127.2, 124.4, 124.2, 120.4, 84.4, 70.9, 70.4, 62.2,
15.1.
HRMS (ESI): m/z calcd for C18H15NO2S + Na (M + Na)+: 332.0716;
found: 332.0723.
All commercially available chemicals and reagents were used with-
out any further purification. 1H and 13C NMR spectra were recorded
at 400 and 100 MHz, respectively, using TMS as the internal stan-
dard and CDCl3 as the solvent. Chemical shifts were expressed in
ppm and J values are given in Hz. High-resolution mass spectra
(HRMS) were obtained using the ESI-TOF method. Flash column
chromatography was carried out using 300–400 mesh silica gel.
(Z)-N-Benzyl-4-methyl-N-(4-phenylbut-3-en-1-ynyl)benzene-
sulfonamide (5a)
Yield: 2.224 g (63%); brown oil.
IR (neat): 3030, 2921, 2211, 1596, 1362, 1165, 720 cm–1.
Preparation of the ynamides was done according to Hsung’s meth-
od.9c Characterization of unreported ynamides is listed below.
1H NMR (400 MHz, CDCl3): δ = 7.76 (2 H, d, J = 8.4 Hz), 7.68–
7.71 (2 H, m), 7.25–7.33 (10 H, m), 6.48 (1 H, d, J = 12.0 Hz), 5.71
(1 H, d, J = 12.0 Hz), 4.60 (2 H, s), 2.42 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 144.8, 136.5, 135.6, 134.8, 134.5,
129.9, 128.7, 128.5, 128.4, 128.3, 128.2, 128.1, 127.6, 106.5, 89.2,
71.0, 55.7, 21.7.
N-Benzyl-N-[2-(2-methoxyphenyl)ethynyl]methanesulfon-
amide (1d)
Yield: 2.924 g (81%); brown oil.
IR (neat): 3032, 2935, 2237, 1704, 1495, 1356, 1162, 756 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.56–7.58 (2 H, m), 7.25–7.42 (5
H, m), 6.84–6.91 (2 H, m), 4.72 (2 H, s), 3.83 (3 H, s), 2.95 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 160.0, 134.8, 132.9, 129.5, 129.2,
HRMS (ESI): m/z calcd for C24H21NO2S + Na (M + Na)+: 410.1185;
found: 410.1190.
128.8, 128.7, 120.5, 111.8, 110.8, 86.1, 68.1, 55.9, 55.8, 38.7.
HRMS (ESI): m/z calcd for C17H17NO3S + Na (M + Na)+: 338.0826;
found: 338.0827.
N-Benzyl-4-methyl-N-(3-phenoxyprop-1-ynyl)benzenesulfon-
amide (5b)
Yield: 4.834 g (87%); brown oil.
tert-Butyl Benzyl-[2-(2-methoxyphenyl)ethynyl]carbamate (1e)
Yield: 5.889 g (75%); brown oil.
IR (neat): 2978, 2245, 1719, 1390, 1248, 1156, 748 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.46–7.48 (2 H, m), 7.18–7.38 (5
H, m), 6.83–6.88 (2 H, m), 4.69 (2 H, s), 3.84 (3 H, s), 1.54 (9 H, s).
13C NMR (100 MHz, CDCl3): δ = 159.2, 153.9, 136.6, 132.3, 128.6,
128.4, 128.3, 127.8, 120.4, 113.1, 110.7, 82.6, 55.7, 53.4, 28.1.
HRMS (ESI): m/z calcd for C21H23NO3 + Na (M + Na)+: 360.1571;
IR (neat): 3032, 2244, 1597, 1494, 1364, 1212, 1168 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.62 (2 H, d, J = 8.0 Hz), 7.16–
7.31 (9 H, m), 6.87–7.01 (3 H, m), 4.74 (2 H, s), 4.44 (2 H, s), 2.40
(3 H, s).
13C NMR (100 MHz, CDCl3): δ = 157.4, 144.7, 134.4, 134.3, 129.7,
129.4, 128.7, 128.6, 128.3, 127.6, 121.2, 115.0, 80.8, 67.3, 55.9,
55.3, 21.7.
HRMS (ESI): m/z calcd for C23H22NO3S (M + H)+: 392.1315;
found: 392.1316.
found: 360.1576.
N-Benzyl-4-methyl-N-{2-[2-(methylthio)phenyl]ethynyl}ben-
zenesulfonamide (3a)
2-Amidobenzofurans 2 and 2-Amidobenzothiophenes 4; N-Ben-
zyl-N-(3-iodobenzofuran-2-yl)-4-methylbenzenesulfonamide
(2a); Typical Procedure
To a solution of 1a (0.5 mmol, 195.7 mg) in CH2Cl2 (4 mL) was
added I2 (0.75 mmol, 190.4 mg, 1.5 equiv). The reaction mixture
was allowed to stir at r.t. After the consumption of 1a (TLC, eluent:
hexane–EtOAc, 9:1), the mixture was concentrated, and the residue
Yield: 0.4922 g (61%); brown oil.
IR (neat): 2920, 2228, 1434, 1361, 1166, 751 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.86 (2 H, d, J = 8.4 Hz), 7.00–
7.40 (11 H, m), 4.63 (2 H, s), 2.43 (3 H, s), 2.41 (3 H, s).
Synthesis 2013, 45, 1975–1982
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes
1979
was purified by flash chromatography on silica gel (eluent: hexane–
EtOAc, 9:1–6:1) to afford 2a; yield: 246.1 mg (97%); pale solid; mp
123–125 °C.
IR (KBr): 3030, 1598, 1447, 1351, 1169, 741, 666 cm–1.
13C NMR (100 MHz, CDCl3): δ = 154.6, 150.9, 140.8, 136.3, 129.5,
129.2, 127.0, 126.2, 125.9, 123.6, 119.1, 111.6, 107.3, 71.2, 61.2.
HRMS (ESI): m/z calcd for C17H12ClNO3 + Na (M + Na)+:
336.0410; found: 336.0403.
1H NMR (400 MHz, CDCl3): δ = 7.83 (2 H, d, J = 8.0 Hz), 7.21–
7.37 (11 H, m), 4.77 (2 H, s), 2.48 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 152.4, 148.0, 144.6, 135.8, 134.4,
130.5, 130.0, 129.1, 128.5, 128.3, 126.5, 123.7, 122.1, 111.5, 67.6,
54.1, 21.8.
HRMS (ESI): m/z calcd for C22H18INO3S + Na (M + Na)+:
525.9966; found: 525.9950.
N-(3-Iodobenzofuran-2-yl)-4-methyl-N-phenylbenzenesulfon-
amide (2g)
Yield: 216.3 mg (88%); pale solid; mp 159–161 °C.
IR (KBr): 3056, 1597, 1446, 1354, 1170, 751, 667 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.28–7.74 (13 H, m), 2.44 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 152.6, 148.8, 144.6, 138.5, 135.8,
130.5, 129.6, 129.4, 128.7, 128.6, 126.7, 123.8, 122.2, 111.7, 67.2,
21.8.
N-Benzyl-N-(3-bromobenzofuran-2-yl)-4-methylbenzenesul-
fonamide (2b)
Yield: 180.8 mg (79%); pale solid; mp 104–106 °C.
IR (KBr): 3035, 1613, 1448, 1358, 1167, 744, 666 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.82 (2 H, d, J = 8.4 Hz), 7.21–
HRMS (ESI): m/z calcd for C21H16INO3S + Na (M + Na)+:
511.9788; found: 511.9793.
N-Benzyl-N-(3-iodobenzofuran-2-yl)methanesulfonamide (2h)
Yield: 165.1 mg (77%); pale solid; mp 144–146 °C.
IR (KBr): 3032, 1602, 1449, 1338, 1159, 797 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.28–7.43 (9 H, m), 4.90 (2 H, s),
7.45 (11 H, m), 4.77 (2 H, s), 2.48 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 151.7, 144.7, 144.6, 135.8, 134.5,
129.9, 128.8, 128.5, 128.2, 128.1, 127.6, 126.4, 123.6, 120.3, 111.6,
97.7, 53.8, 21.7.
HRMS (ESI): m/z calcd for C22H18BrNO3S + Na (M + Na)+:
478.0090; found: 478.0088.
3.13 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 152.5, 148.2, 134.6, 130.4, 129.3,
128.7, 128.5, 126.7, 123.9, 122.2, 111.6, 67.1, 54.9, 41.2.
HRMS (ESI): m/z calcd for C16H14INO3S + Na (M + Na)+:
449.9632; found: 449.9637.
N-Benzyl-N-(3-chlorobenzofuran-2-yl)-4-methylbenzenesul-
fonamide (2c)
Yield: 133.6 mg (65%); pale solid; mp 112–114 °C.
IR (KBr): 3064, 1450, 1358, 1168, 740, 667 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.81 (2 H, d, J = 8.4 Hz), 7.20–
tert-Butyl Benzyl(3-iodobenzofuran-2-yl)carbamate (2i)
Yield: 167.0 mg (74%); pale solid; mp 101–103 °C.
IR (KBr): 2977, 1715, 1610, 1379, 1152, 760 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.27–7.42 (9 H, m), 4.89 (2 H, s),
7.49 (11 H, m), 4.75 (2 H, s), 2.48 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 151.1, 144.6, 143.0, 135.8, 134.5,
129.9, 128.6, 128.5, 128.2, 128.1, 126.3, 126.1, 123.5, 119.4, 111.7,
110.7, 53.6, 21.7.
HRMS (ESI): m/z calcd for C22H18ClNO3S + Na (M + Na)+:
434.0593; found: 434.0594.
1.49 (9 H, s).
13C NMR (100 MHz, CDCl3): δ = 153.1, 151.9, 151.0, 136.9, 130.8,
128.5, 128.4, 127.7, 125.6, 123.5, 121.5, 111.4, 82.2, 62.4, 52.3,
28.3.
HRMS (ESI): m/z calcd for C20H20INO3 + Na (M + Na)+: 472.0380;
found: 472.0386.
3-(3-Iodobenzofuran-2-yl)-4-phenyloxazolidin-2-one (2d)
Yield: 185.5 mg (92%); pale solid; mp 157–159 °C.
N-Allyl-N-(3-bromobenzofuran-2-yl)-4-methylbenzenesulfon-
amide (2j)
Yield: 111.3 mg (55%); pale solid; mp 83–85 °C.
IR (KBr): 2918, 1616, 1448, 1354, 1164, 754, 674 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.78 (2 H, d, J = 8.4 Hz), 7.29–
7.52 (6 H, m), 5.75–5.85 (1 H, m), 5.04–5.18 (2 H, m), 4.18–4.20 (2
H, m), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 151.7, 144.8, 144.5, 135.8, 131.4,
129.8, 128.1, 127.6, 126.4, 123.6, 120.3, 119.9, 111.7, 97.5, 52.8,
21.7.
IR (KBr): 2969, 1759, 1617, 1394, 1205, 1040, 757 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.46–7.48 (2 H, m), 7.19–7.36 (7
H, m), 5.59 (1 H, dd, J = 8.4 Hz), 4.87 (1 H, dd, J = 8.4 Hz), 4.37 (1
H, dd, J = 8.4 Hz).
13C NMR (100 MHz, CDCl3): δ = 154.5, 152.1, 146.0, 136.3, 130.4,
129.5, 129.2, 127.3, 126.1, 123.8, 121.5, 111.4, 71.1, 62.6, 61.4.
HRMS (ESI): m/z calcd for C17H12INO3 + Na (M + Na)+: 427.9751;
found: 427.9760.
HRMS (ESI): m/z calcd for C18H16BrNO3S + Na (M + Na)+:
429.9927; found: 429.9911.
3-(3-Bromobenzofuran-2-yl)-4-phenyloxazolidin-2-one (2e)
Yield: 132.7 mg (74%); pale solid; mp 121–123 °C.
IR (KBr): 2968, 1760, 1630, 1396, 1205, 1048, 757 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.22–7.46 (9 H, m), 5.55 (1 H, dd,
J = 8.4 Hz), 4.88 (1 H, dd, J = 8.4 Hz), 4.37 (1 H, dd, J = 8.4 Hz).
13C NMR (100 MHz, CDCl3): δ = 154.5, 151.5, 142.5, 136.3, 129.5,
129.2, 127.6, 127.1, 126.0, 123.7, 119.9, 111.5, 93.8, 71.2, 61.2.
N-(3-Iodobenzofuran-2-yl)-4-methyl-N-propylbenzenesulfon-
amide (2k)
Yield: 128.9 mg (57%); pale solid; mp 110–112 °C.
IR (KBr): 2966, 1597, 1447, 1355, 1167, 746, 665 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.77 (2 H, d, J = 8.4 Hz), 7.30–
7.43 (6 H, m), 3.53 (2 H, t, J = 8.4 Hz), 2.46 (3 H, s), 1.47–1.56 (2
H, m), 0.92 (3 H, t, J = 8.4 Hz).
HRMS (ESI): m/z calcd for C17H12BrNO3 + Na (M + Na)+:
379.9892; found: 379.9898.
13C NMR (100 MHz, CDCl3): δ = 152.4, 148.3, 144.3, 135.8, 130.6,
129.8, 128.2, 126.5, 123.7, 122.1, 111.5, 67.1, 52.1, 21.71, 21.70,
11.2.
HRMS (ESI): m/z calcd for C18H18INO3S + Na (M + Na)+:
477.9958; found: 477.9950.
3-(3-Chlorobenzofuran-2-yl)-4-phenyloxazolidin-2-one (2f)
Yield: 136.2 mg (87%); pale solid; mp 125–127 °C.
IR (KBr): 2919, 1775, 1641, 1395, 1210, 1053, 757 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.22–7.49 (9 H, m), 5.53 (1 H, dd,
J = 8.4 Hz), 4.89 (1 H, dd, J = 8.4 Hz), 4.37 (1 H, dd, J = 8.4 Hz).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1975–1982

1980
Y. Kong et al.
PAPER
3-(5-Bromo-3-iodobenzofuran-2-yl)-4-phenyloxazolidin-2-one
N-(3-Bromobenzo[b]thiophen-2-yl)-4-methyl-N-phenylben-
(2l)
zenesulfonamide (4d)
Yield: 187.1 mg (77%); brown oil.
Yield: 139.2 mg (63%); pale solid; mp 164–166 °C.
IR (neat): 2917, 1767, 1610, 1390, 1205, 1044, 729 cm–1.
IR (KBr): 2922, 2851, 1361, 1166, 1089, 754, 692 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.28–7.44 (7 H, m), 7.15 (1 H, d,
J = 8.8 Hz), 5.57 (1 H, dd, J = 8.8 Hz), 4.89 (1 H, dd, J = 8.8 Hz),
4.38 (1 H, dd, J = 8.8 Hz).
13C NMR (100 MHz, CDCl3): δ = 154.1, 150.8, 147.0, 135.9, 132.3,
129.6, 129.3, 128.9, 127.2, 124.2, 116.9, 112.9, 71.1, 61.3, 61.1.
1H NMR (400 MHz, CDCl3): δ = 7.69–7.78 (4 H, m), 7.29–7.51 (9
H, m), 2.54 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 144.6, 139.9, 137.2, 136.9,
135.83, 135.78, 129.6, 129.3, 128.8, 128.6, 128.3, 126.7, 125.4,
124.2, 122.6, 111.2, 21.7.
HRMS (ESI): m/z calcd for C17H11BrINO3 + Na (M + Na)+:
HRMS (ESI): m/z calcd for C21H16BrNO2S2 + Na (M + Na)+:
505.8859; found: 505.8858.
479.9698; found: 479.9707.
3-(3-Iodo-5-methylbenzofuran-2-yl)-4-phenyloxazolidin-2-one
3-(3-Bromobenzo[b]thiophen-2-yl)-4-phenyloxazolidin-2-one
(2m)
(4e)
Yield: 174.0 mg (83%); brown oil.
Yield: 164.7 mg (88%); brown oil.
IR (neat): 2918, 1768, 1390, 1205, 1043, 699 cm–1.
IR (neat): 2920, 1759, 1389, 1182, 1035, 751 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.47 (2 H, m), 7.28–7.37 (3
H, m), 7.19 (1 H, d, J = 8.4 Hz), 7.08 (2 H, d, J = 8.4 Hz), 5.57 (1
H, dd, J = 8.4 Hz), 4.86 (1 H, dd, J = 8.4 Hz), 4.36 (1 H, dd, J = 8.4
Hz), 2.38 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 154.4, 150.5, 145.9, 136.2, 133.4,
130.4, 129.5, 129.2, 127.3, 127.28, 121.3, 111.0, 71.1, 62.4, 61.4,
21.3.
1H NMR (400 MHz, CDCl3): δ = 7.72 (1 H, d, J = 8.0 Hz), 7.58 (1
H, d, J = 8.0 Hz), 7.29–7.41 (7 H, m), 5.51 (1 H, dd, J = 8.0 Hz),
4.89 (1 H, dd, J = 8.0 Hz), 4.41 (1 H, dd, J = 8.0 Hz).
13C NMR (100 MHz, CDCl3): δ = 155.3, 136.6, 136.2, 135.9, 133.4,
129.5, 129.3, 127.4, 126.2, 125.3, 123.3, 122.5, 106.5, 70.8, 62.6.
HRMS (ESI): m/z calcd for C17H12BrNO2S + Na (M + Na)+:
395.9664; found: 395.9663.
HRMS (ESI): m/z calcd for C18H14INO3 + Na (M + Na)+: 441.9911;
found: 441.9903.
N-Benzyl-N-(2-iodonaphthalen-1-yl)-4-methylbenzenesulfon-
amide (6a); Typical Procedure
To a solution of 5a (0.609 mmol, 236.2 mg) in CH2Cl2 (4 mL) was
added I2 (0.671 mmol, 170.2 mg, 1.1 equiv) and K2CO3 (1.218
mmol, 169.3 mg, 2.0 equiv). The reaction mixture was allowed to
stir at r.t. After the consumption of 5a (TLC, eluent: hexane–
EtOAc, 9:1), the mixture was filtered over a plug of silica gel,
washed with EtOAc (50 mL), and the filtrate was concentrated. The
residue was purified by flash chromatography on silica gel (eluent:
hexane–EtOAc, 9:1–6:1) to afford 6a; yield: 163.0 mg (64%);
brown oil.
N-Benzyl-N-(3-iodobenzo[b]thiophen-2-yl)-4-methylbenzene-
sulfonamide (4a)
Yield: 233.7 mg (90%); brown oil.
IR (neat): 2920, 1354, 1161, 1088, 812, 741 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.80 (2 H, d, J = 8.0 Hz), 7.23–
7.69 (11 H, m), 4.85 (2 H, s), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 144.5, 140.0, 138.8, 137.9, 135.6,
134.6, 129.9, 129.5, 128.5, 128.4, 128.3, 126.7, 126.5, 125.4, 122.6,
86.4, 56.4, 21.8.
HRMS (ESI): m/z calcd for C22H18INO2S2 + Na (M + Na)+:
541.9716; found: 541.9718.
IR (neat): 3031, 2923, 1344, 1157, 1088, 1036, 774 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.70–7.86 (4 H, m), 7.31–7.53 (5
H, m), 7.05–7.20 (6 H, m), 5.04 (1 H, d, J = 14.0 Hz), 4.90 (1 H, d,
J = 14.0 Hz), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 143.8, 138.56, 138.48, 136.5,
134.8, 134.6, 133.9, 130.6, 130.2, 129.7, 128.4, 128.1, 127.7,
126.64, 126.56, 125.5, 100.5, 54.9, 21.7.
N-Benzyl-N-(3-bromobenzo[b]thiophen-2-yl)-4-methylben-
zenesulfonamide (4b)
Yield: 214.0 mg (91%); brown oil.
IR (neat): 2922, 1432, 1354, 1162, 1089, 812, 748 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.80 (2 H, d, J = 8.0 Hz), 7.23–
HRMS (ESI): m/z calcd for C24H21INO2S (M + H)+: 514.0332;
found: 514.0320.
7.72 (11 H, m), 4.87 (2 H, s), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 144.4, 137.0, 136.4, 135.9, 135.7,
134.8, 129.9, 129.2, 128.5, 128.3, 128.2, 126.5, 125.2, 124.0, 122.6,
110.5, 55.8, 21.7.
N-Benzyl-N-(2-bromonaphthalen-1-yl)-4-methylbenzenesul-
fonamide (6b)
Yield: 146.6 mg (69%); brown oil.
IR (neat): 2923, 2853, 1345, 1159, 1089, 810, 775 cm–1.
HRMS (ESI): m/z calcd for C22H18BrNO2S2 + Na (M + Na)+:
1H NMR (400 MHz, CDCl3): δ = 7.79 (2 H, d, J = 8.4 Hz), 7.54–
7.72 (4 H, m), 7.25–7.41 (4 H, m), 7.05–7.12 (5 H, m), 5.09 (1 H, d,
J = 14.0 Hz), 4.79 (1 H, d, J = 14.0 Hz), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 143.7, 138.2, 135.0, 134.9, 134.3,
133.2, 130.33, 130.29, 130.2, 129.6, 128.2, 128.1, 128.0, 127.6,
126.9, 126.4, 125.4, 123.6, 54.3, 21.7.
493.9855; found: 493.9856.
N-Benzyl-N-(3-chlorobenzo[b]thiophen-2-yl)-4-methylben-
zenesulfonamide (4c)
Yield: 161.5 mg (75%); pale solid; mp 155–157 °C.
IR (KBr): 2922, 1353, 1162, 1089, 935, 750 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79 (2 H, d, J = 8.0 Hz), 7.23–
HRMS (ESI): m/z calcd for C24H20BrNO2S + K (M + K)+:
504.0030; found: 504.0033.
7.72 (11 H, m), 4.85 (2 H, s), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 144.4, 136.2, 135.7, 134.9, 134.6,
134.4, 129.8, 129.0, 128.5, 128.2, 126.4, 125.0, 122.7, 122.5, 121.6,
55.6, 21.7.
HRMS (ESI): m/z calcd for C22H18ClNO2S2 + Na (M + Na)+:
450.0360; found: 450.0355.
N-Benzyl-N-(3-iodo-2H-chromen-4-yl)-4-methylbenzenesul-
fonamide (6c)
Yield: 100.1 mg (39%); brown oil.
IR (neat): 2922, 2852, 1599, 1453, 1347, 1159, 938 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.88 (2 H, d, J = 8.4 Hz), 7.34 (2
H, d, J = 8.4 Hz), 7.09–7.25 (6 H, m), 6.69–6.84 (3 H, m), 4.96 (1
Synthesis 2013, 45, 1975–1982
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Amidobenzofurans and 2-Amidobenzothiophenes
1981
H, d, J = 14.8 Hz), 4.84 (1 H, d, J = 14.8 Hz), 4.75 (1 H, d, J = 14.8
Hz), 4.54 (1 H, d, J = 14.8 Hz), 2.47 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 154.2, 144.0, 138.2, 137.8, 134.6,
130.3, 130.1, 129.7, 128.3, 125.0, 121.9, 121.4, 115.9, 95.0, 75.7,
53.1, 21.7.
HRMS (ESI): m/z calcd for C23H20INO3S + K (M + K)+: 555.9840;
found: 555.9861.
IR (KBr): 2949, 1707, 1641, 1351, 1270, 1157, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.74 (1 H, d, J = 7.6 Hz), 7.25–
7.48 (9 H, m), 6.46 (1 H, d, J = 16.4 Hz), 4.86 (2 H, s), 3.79 (3 H,
s), 3.11 (3 H, s).
13C NMR (100 MHz, CDCl3): δ = 166.9, 152.3, 147.8, 134.2, 133.4,
129.2, 128.7, 128.6, 126.2, 125.2, 124.1, 121.3, 119.8, 114.5, 111.6,
55.1, 51.7, 40.3.
HRMS (ESI): m/z calcd for C20H19NO5S + Na (M + Na)+: 408.0876;
found: 408.0879.
4-Phenyl-3-(3-phenylbenzofuran-2-yl)oxazolidin-2-one (7a)
A vial was charged with 2d (0.25 mmol, 101.3 mg), NaBPh4
(0.0625 mmol, 21.4 mg), Pd(OAc)2 (0.0125 mmol, 3.2 mg), and
Na2CO3 (0.25 mmol, 26.5 mg). The vial was evacuated under high
vacuum and backfilled with N2. DMF–H2O (1:0.5 mL) was added
next and the solution was stirred at 100 °C. After the consumption
of 2d (TLC, eluent: hexane–EtOAc, 6:1), the mixture was filtered
over a plug of silica gel and washed with EtOAc (50 mL). The fil-
trate was washed with brine (50 mL), dried (Na2SO4), filtered, and
concentrated. The residue was purified by flash chromatography on
silica gel (eluent: hexane–EtOAc, 6:1) to afford 7a; yield: 81.5 mg
(92%); brown oil.
Acknowledgment
We are grateful to the National Natural Science Foundation of
China (Project No. 21102029) for financial support.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
IR (neat): 3061, 1767, 1453, 1394, 1210, 1043, 750, 699 cm–1.
References
1H NMR (400 MHz, CDCl3): δ = 7.30–7.53 (8 H, m), 7.01–7.23 (6
H, m), 5.23 (1 H, dd, J = 8.8 Hz), 4.76 (1 H, dd, J = 8.8 Hz), 4.27 (1
H, dd, J = 8.8 Hz).
(1) (a) Kirilmis, C.; Ahmedzade, M.; Servi, S.; Koca, M.;
Kizirgil, A.; Kazaz, C. Eur. J. Med. Chem. 2008, 43, 300.
(b) Schultz, D. M.; Prescher, J. A.; Kidd, S.; Marona-
Lewicka, D.; Nichols, D. E.; Monte, A. Bioorg. Med. Chem.
2008, 16, 6242. (c) Ando, K.; Kawamura, Y.; Akai, Y.;
Kunitomo, J.; Yokomizo, T.; Yamashita, M.; Ohta, S.;
Ohishi, T.; Ohishi, Y. Org. Biomol. Chem. 2008, 6, 296.
(d) Dixit, M.; Tripathi, B. K.; Tamrakar, A. K.; Srivastava,
A. K.; Kumar, B.; Goel, A. Bioorg. Med. Chem. 2007, 15,
727.
13C NMR (100 MHz, CDCl3): δ = 156.6, 152.2, 140.7, 135.8, 130.5,
129.1, 128.9, 128.83, 128.81, 128.0, 127.8, 127.2, 125.3, 123.1,
120.4, 117.5, 111.5, 70.8, 62.0.
HRMS (ESI): m/z calcd for C23H17NO3 + Na (M + Na)+: 378.1101;
found: 378.1104.
4-Phenyl-3-[3-(2-phenylethynyl)benzofuran-2-yl]oxazolidin-2-
one (7b)
(2) (a) Su, T.; Naughton, M. A. H.; Smyth, M. S.; Rose, J. W.;
Arfsten, A. E.; McCowan, J. R.; Jakubowski, J. A.; Wyss, V.
L.; Ruterbories, K. J.; Sall, D. J.; Scarborough, R. M. J. Med.
Chem. 1997, 40, 4308. (b) Takeuchi, K.; Kohn, T. J.;
Bastian, J. A.; Chirgadze, N. Y.; Denney, M. L.; Harper, R.
W.; Lin, H.; Mccowan, J. R.; Gifford-Moore, D. S.; Richett,
M. E.; Sall, D. J.; Smith, G. F.; Zhang, M. Bioorg. Med.
Chem. Lett. 1999, 9, 759.
(3) For electrophilic cyclization chemistry, see: (a) Yue, D.;
Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292.
(b) Cho, C.-H.; Neuenswander, B.; Lushington, G.; Larock,
R. C. J. Comb. Chem. 2008, 10, 941. (c) Manarin, F.;
Roehrs, J. A.; Mozzaquatro Gay, R.; Brandão, R.; Menezes,
P. H.; Nogueira, C. W.; Zeni, G. J. Org. Chem. 2009, 74,
2153. (d) Yao, T.; Yue, D.; Larock, R. C. J. Org. Chem.
2005, 70, 9985. (e) Mehta, S.; Waldo, J. P.; Larock, R. C.
J. Org. Chem. 2009, 74, 1141. (f) Mehta, S.; Larock, R. C.
J. Org. Chem. 2010, 75, 1652. (g) Godoi, B.; Schumacher,
R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937.
A vial was charged with 2d (0.5 mmol, 202.5 mg), PdCl2(PPh3)2
(0.025 mmol, 17.5 mg), and CuI (0.0125 mmol, 2.4 mg). The vial
was evacuated under high vacuum and backfilled with N2. Et3N–
THF (4:4 mL) and phenylacetylene (0.75 mmol, 76.6 mg) were add-
ed next and the solution was stirred at r.t. After the consumption of
2d (TLC, eluent: hexane–EtOAc, 6:1), the mixture was filtered over
a plug of silica gel and washed with EtOAc (50 mL). The filtrate
was concentrated and the residue was purified by flash chromatog-
raphy on silica gel (eluent: hexane–EtOAc, 6:1) to afford 7b; yield:
188.1 mg (99%); brown oil.
IR (neat): 3061, 1771, 1454, 1205, 1045, 749 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.59–7.63 (3 H, m), 7.23–7.47 (11
H, m), 5.74 (1 H, dd, J = 8.0 Hz), 4.90 (1 H, dd, J = 8.0 Hz), 4.37 (1
H, dd, J = 8.0 Hz).
13C NMR (100 MHz, CDCl3): δ = 154.3, 151.4, 147.2, 136.8, 131.7,
129.3, 129.2, 128.7, 128.5, 128.1, 126.8, 125.3, 123.6, 123.0, 120.3,
111.3, 97.1, 96.9, 78.0, 71.1, 61.1.
HRMS (ESI): m/z calcd for C25H17NO3 + Na (M + Na)+: 402.1101;
found: 402.1109.
(4) (a) Makovetskii, V. P.; Dzvinchuk, I. B.; Yaremko, V. V.;
Svishchuk, A. A. Ukr. Khim. Zh. 1979, 45, 652; Chem.
Abstr. 1979, 91, 140672. (b) King, T. J.; Newall, C. E.
J. Chem. Soc. 1965, 974.
Methyl (E)-3-[2-(N-Benzylmethylsulfonamido)benzofuran-3-
yl]acrylate (7c)
A vial was charged with 2h (0.25 mmol, 106.8 mg), Pd(OAc)2
(0.0125 mmol, 3.2 mg), Na2CO3 (0.25 mmol, 26.5 mg), and n-
Bu4NCl (0.25 mmol, 55.2 mg). The vial was evacuated under high
vacuum and backfilled with N2. DMF (1 mL) and methyl acrylate
(0.525 mmol, 45.2 mg) were added next and the solution was stirred
at 80 °C. After the consumption of 2h (TLC, eluent: hexane–
EtOAc, 6:1), the mixture was filtered over a plug of silica gel and
washed with EtOAc (50 mL). The filtrate was washed with brine
(50 mL), dried (Na2SO4), filtered, and concentrated. The residue
was purified by flash chromatography on silica gel (eluent: hexane–
EtOAc, 6:1) to afford 7c; yield: 45.9 mg (48%); pale solid; mp 154–
156 °C.
(5) Tatsumi, R.; Fujio, M.; Satoh, H.; Katayama, J.; Takanashi,
S.; Hashimoto, K.; Tanaka, H. J. Med. Chem. 2005, 48,
2678.
(6) For the synthesis of 2-amidobenzofurans, see:
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