A facile construction of oxygen heterocycles by the reaction of benzoxepine-4-carboxylates with dihaloalkanes
and activated alkynesKasagani Veera Prasad, Kurma Siva Hariprasad, Bhimapaka China Raju*
Organic Synthesis and Process Chemistry Division,
CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
E-mail: [email protected]
Homepage: http://www.iictindia.org
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2019
Supporting Information
1. General information S2
2. General Procedure for the preparation of benzoxepine-4-carboxylates &
Spectrums S2-S5
3. 1H & 13C NMR spectras of Naphthoate S6-S7
4. Optimization of reaction conditions for the preparation of 8a S7
3. 1H NMR, 13C NMR and HRMS spectras of the compounds S8-S60
1. General information:
Salicylaldehydes and ethyl 4-chloro-3-oxobutanoate were procured from Sigma-Aldrich.
Triphenylphosphine, 2-bromopropionate, dichloromethane, 1,2-dichloroethane, 1,3-
dibromopropane, 1,4-dibromobutane, TBAB, KHCO3, 18-crown-6, TBAI and solvents were
obtained from local suppliers. 1H NMR and 13C NMR spectra were recorded on a Avance 400
MHz and 500 MHz spectrometer in CDCl3 using TMS as internal standard. IR spectra were
recorded on a Nicollet 740 FTIR spectrometer. Mass spectra were obtained on Agilent LCMS
instrument. HRMS were measured on Agilent Technologies 6510, Q-TOFLC/MS ESI-
Technique. Melting points were determined in open glass capillary tubes on a Stuart melting
point apparatus and are uncorrected. All reactions were monitored by thin layer
chromatography (TLC) on pre-coated silica gel 60 F254 (mesh); spots were visualized under
UV light. Merck silica gel (60-120 mesh) was used for chromatography.
2. General Procedure for the reparation of benzoxepine-4-carboxylates 1a-h: A mixture
of ethyl 2-(chloromethyl)-2-hydroxy-2H-chromene-3-carboxylate (268 mg, 1.0 mmol) and
(1-ethoxycarbonylethylidene)triphenylphosphorane (506 mg, 1.4 mmol) in dry CH2Cl2 (4
mL) were stirred at the room temperature for 6 h (TLC) under nitrogen atmosphere. After
completion of the reaction (TLC), the solvent was evaporated under reduced pressure, crude
residue was purified by column chromatography (hexane/ethyl acetate 9:1) afforded (E)-ethyl
3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate 1a (190 mg, 90% yield) as yellow liquid.
The remaining benzoxepine compounds 1b-h have been prepared by the reaction of 2H-
chromene-3-carboxylates with Wittig salt.
(E)-Ethyl 3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1a):
Pale yellow liquid, Yield: 90%; FT-IR (KBr): 3451, 2981, 2925, 1728, 1675, 1605, 1565,
1482, 1447, 1394, 1284, 1250, 1189, 1115, 1041 cm-1. 1H NMR (CDCl3) : δ 1.33 (t, J = 6.9
Hz, 3H, CH3), 4.34 (q, J = 6.9 Hz, 2H, OCH2), 4.58 (s, 2H, OCH2), 7.12-7.24 (m, 2H,
aromatic), 7.38-7.52 (m, 2H, aromatic), 7.89 (s, 1H, aromatic) ppm. 13C NMR (CDCl3): δ
14.21, 61.28, 78.15, 120.46, 124.25, 125.7, 132.14, 133.45, 134.87, 145.39, 159.46, 165.30,
191.50 ppm. MS-ESI: 233 [M+H]+, 255 [M+Na]+. HRMS-ESI: Calcd for C13H13O4 [M+H]+
233.0808; found 233.0812.
(E)-Ethyl 7-bromo-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1b):
Colourless solid, Yield: 73%; FT-IR (KBr): 2923, 2854, 2854, 1711, 1680, 1605, 1474,
1379, 1285, 1255, 1224, 1191, 1115, 1038 cm-1. 1H NMR (CDCl3) : δ 1.38 (t, J = 7.0 Hz, 3H,
CH3), 4.33 (q, J = 7.0 Hz, 2H, OCH2), 4.57 (s, 2H, OCH2), 7.05 (d, J = 8.7 Hz, 1H, aromatic),
7.50 (dd, J = 2.5, J = 8.7 Hz, 1H, aromatic), 7.63 (d, J = 2.0 Hz, 1H, aromatic), 7.77 (s, 1H,
aromatic) ppm. 13C NMR (CDCl3): δ 14.26, 61.90, 78.54, 116.92, 122.58, 127.46, 131.74,
136.43, 136.82, 144.01, 158.48, 165.21, 192.10 ppm. MS-ESI: 333, 335 [M+Na]+. HRMS-
ESI : Calcd for C13H11BrO4Na [M+Na]+ 332.9733; found 332.9741.
(E)-Ethyl 7-chloro-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1c):
Colourless solid, Yield: 88%; FT-IR (KBr) : 2922, 1714, 1681, 1607, 1477, 1384, 1274,
1193, 1105 cm-1.1H NMR (CDCl3): δ 1.37 (t, J = 7.3 Hz, 3H, CH3), 4.32 (q, J = 7.3 Hz, 2H,
OCH2), 4.56 (s, 2H, OCH2), 7.09 (d, J = 8.5 Hz, 1H, aromatic), 7.35 (d, J = 8.5 Hz, 1H,
aromatic), 7.47 (s, 1H, aromatic), 7.76 (s, 1H, aromatic) ppm. 13C NMR (CDCl3) : δ 14.26,
61.84, 78.40, 122.18, 126.80, 129.60, 130.52, 133.34, 133.81, 143.75, 157.96, 165.01, 191.81
ppm. MS-ESI: 267, 269[M+H]+, 289, 291 [M+Na]+. HRMS-ESI : Calcd for C13H11ClO4Na
[M+Na]+ 289.0238; found 289.0236.
(E)-Ethyl 3-oxo-7-phenyl-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1d): The title
compound 1d was prepared by the reaction of ethyl 2-(chloromethyl)-2-hydroxy-6-phenyl-
2H-chromene-3-carboxylate (1.0 mmol) with Ph3P=C(CH3)CO2C2H5 (3.0 mmol). The crude
compound was directly utilized for the further reaction, since the compound was rearranging
in to its corresponding ethyl 3,4-dihydroxy-2-naphthoate during the column chromatography.
(E)-Ethyl 7-methoxy-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1e):
Pale yellow liquid, Yield: 80%; FT-IR (KBr): 2924, 1729, 1675, 1607, 1571, 1496, 1464,
1389, 1244, 1209, 1164, 1039 cm-1. 1H NMR (CDCl3): δ 1.38 (t, J = 7.0 Hz, 3H, CH3), 3.81
(s, 3H, OCH3), 4.32 (q, J = 7.0 Hz, 2H, OCH2), 4.54 (s, 2H, OCH2), 6.91-6.98 (m, 2H,
aromatic), 7.06 (d, J = 8.8 Hz, 1H, aromatic), 7.80 (s, 1H, aromatic) ppm. 13C NMR (CDCl3):
δ 14.29, 55.70, 61.62, 79.21, 117.64, 120.05, 121.67, 126.46, 128.13, 132.66, 145.24, 153.50,
155.91, 165.50 ppm. MS-ESI: 263 [M+H]+, 285 [M+Na]+. HRMS-ESI: Calcd for
C14H14O5Na [M+Na]+5.0733; found 285.0726.
(E)-Ethyl 8-methoxy-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1f): Pale yellow
liquid, Yield: 61%; FT-IR (KBr): 3056, 2986, 1728, 1671, 1608, 1438, 1186, 1119, 1027
cm-1. 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 7.1 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 6.76
(dd, J = 8.7, 2.5 Hz, 1H), 6.67 (d, J = 2.4 Hz, 1H), 4.58 (s, 2H), 4.39-4.29 (m, 2H), 3.87 (s,
3H), 1.42-1.34 (m, 3H) ppm. 13C NMR (126 MHz, CDCl3): δ 191.0, 165.9, 164.6, 161.8,
147.3, 137.2, 128.4, 118.3, 111.5, 104.8, 77.7, 61.5, 55.8, 14.2 ppm. MS-ESI: m/z 263
[M+H]+; HRMS-ESI: calcd for C14H15O5 [M+H]+ 263.0914; found 263.0906.
(E)-Ethyl 7-methyl-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1g):
Pale yellow liquid, Yield: 61%; FT-IR (KBr): 2921, 1728, 1673, 1606, 1570, 1494, 1462,
1390, 1241, 1201, 1163, 1036 cm-1. 1H NMR (CDCl3): δ 1.37 (t, J = 7.0 Hz, 3H, CH3), 2.54
(s, 3H, CH3), 4.28 (q, J = 7.0 Hz, 2H, OCH2), 4.52 (s, 2H, OCH2), 6.90-6.97 (m, 2H,
aromatic), 7.03 (d, J = 8.8 Hz, 1H, aromatic), 7.75 (s, 1H, aromatic) ppm. 13C NMR (CDCl3):
δ 14.18, 54.74, 61.16, 78.25, 116.40, 119.02, 121.21, 126.28, 127.94, 132.18, 145.12, 153.08,
154.91, 165.30 ppm. MS-ESI: 247 [M+H]+. HRMS-ESI: Calcd for C14H14O4Na [M+Na]+
269.0813; found 269.0826.
(E)-Ethyl- 9-methyl-3-oxo-2,3-dihydrobenzo[b]oxepine-4-carboxylate (1h):
Yellow colour liquid; Yield: 72%; FT-IR (KBr): 2924, 1729, 1672, 1604, 1573, 1491, 1460,
1391, 1241, 1207, 1165, 1034 cm-1. 1H NMR (CDCl3): δ 7.89 (s, 1H, aromatic), 7.26 (d, J =
7.7 Hz, 2H, aromatic), 7.03 (t, J = 7.6 Hz, 1H, aromatic), 4.55-4.52 (q, J = 7.0 Hz, 2H,
OCH2), 4.32-4.24 (m, 2H, OCH2), 2.24 (s, 3H, CH3), 1.33-1.27 (t, J = 7.0 Hz, 3H, CH3) ppm. 13C NMR (CDCl3) : δ 193.00, 165.81, 157.87, 146.65, 135.45, 132.88, 131.56, 129.96,
125.65, 124.04, 78.30, 61.69, 16.12, 14.25 ppm. MS-ESI : 247 [M+H]+.
3. 1H NMR & 13C NMR spectras of Naphthoate
Intermediate compound Naphthoate
0011223344556677889910101111
1.0 1.0 1.0
1.1
1.1
1.0
2.0
3.0
1.0
30-07.13-238-BCR-CATECHOL
CO2C2H5
OHOH
-1-10011223344556677889910101111
1.8 2.0
3.2
1.0
2.2
05.07.13-212-BCR-DO-CAT
CO2C2H5
ODOD
1H NMR Spectrum of D2O exchange Naphthoate compound
13C NMR Spectrum of intermediate Naphthoate compound
4. Optimization of reaction conditions for the preparation of 8a
Entry Base (equiv.) Time [h] Yieldc
01a
02a
03a
05a
06a
08a
13a
11a
12a
KHCO3 (3.0)KHCO3 (3.0)
KHCO3 (3.0)
KHCO3 (3.0)
Et3N (2.0)DBU (2.0)
Cs2CO3 (3.0)K2CO3 (3.0)
1624
1618
18
2012
1618
0800
1219
24
1000
05
____________________________________________________________________
____________________________________________________________________
____________________________________________________________________
Additive (equiv.)
TBAB (1.0)TPP (1.0)
TBAB (1.0)TBAB (1.0)
------
------
a Reflux, bRoom temperature,c Isolated yield.
05
O
CO2C2H5
O O
O
CO2C2H5
+
CO2C2H5
CO2C2H5
CO2C2H5
CO2C2H5
1a 7a 8a
Solvent
MeCN
EtOHtert-Butanol
---
KHCO3 (3.0)
tert-Butanol
tert-Butanoltert-Butanoltert-Butanoltert-Butanol
10aNaHCO3 (3.0) 24 17--- tert-Butanol09bKHCO3 (3.0) 32 05tert-Butanol
07aKHCO3 (3.0) 16 1118-Crown-6 (1.0) tert-Butanol
---
04aKHCO3 (3.0) 14 05TBAB (1.0) Toluene
MeCN
5. 1H-NMR, 13C-NMR and HRMS Spectras of target compounds 3a-g, 4a-h, 4ha, 5a-c,
6a-c, 8a-f
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.25
2.16
2.13
1.06
1.07
0.99
1.10
1.00
0.00
1.43
1.45
1.46
4.44
4.45
4.47
4.48
6.29
7.26
7.36
7.36
7.36
7.37
7.38
7.50
7.50
7.51
7.51
7.51
7.53
7.79
7.85
7.87
8.09
1H-NMR Spectrum of compound 3a
0102030405060708090100110120130140150160170
14.4
1
61.3
1
76.7
977
.05
77.3
0
102.
53
114.
53
119.
7312
1.65
124.
2412
4.77
128.
2212
8.95
129.
49
142.
49
164.
58
13C-NMR Spectrum of compound 3a
O
O
CO2C2H5
O
O
CO2C2H5
O
O
CO2C2H5
HRMS Spectrum of Compound 3a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0
3.19
2.16
2.14
1.01
1.02
1.00
1.04
0.00
1.42
1.44
1.46
4.43
4.45
4.47
4.48
6.29
7.26
7.56
7.57
7.66
7.68
7.98
8.01
8.02
1H-NMR Spectrum of compound 3b
-100102030405060708090100110120130140150160170
14.3
8
61.4
9
76.7
477
.05
77.3
7
102.
82
115.
4311
8.53
119.
7912
1.50
123.
14
129.
7913
1.23
131.
45
142.
8714
2.97
164.
17
13C-NMR Spectrum of compound 3b
O
O
CO2C2H5
Br
O
O
CO2C2H5
Br
HRMS Spectrum of Compound 3b
O
O
CO2C2H5
Br
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.11
2.18
2.21
1.00
1.01
1.01
1.00
0.00
1.43
1.44
1.46
4.44
4.45
4.46
4.48
7.26
7.42
7.43
7.44
7.44
7.73
7.75
7.83
7.83
7.98
1H-NMR Spectrum of compound 3c
0102030405060708090100110120130140150160170
14.3
8
61.4
8
76.7
377
.05
77.3
6
102.
79
115.
4911
9.65
121.
4912
3.14
127.
9012
9.11
129.
3413
0.53
142.
85
164.
22
13C-NMR Spectrum of compound 3c
O
O
CO2C2H5
Cl
O
O
CO2C2H5
Cl
HRMS Spectrum of compound 3c
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.15
2.12
1.02
2.08
2.07
1.05
1.02
1.04
1.00
0.00
1.44
1.45
1.47
4.44
4.46
4.48
4.50
6.30
7.26
7.37
7.39
7.40
7.47
7.49
7.51
7.67
7.69
7.78
7.80
7.86
7.88
8.05
8.15
1H-NMR Spectrum of compound 3d
O
O
CO2C2H5
Cl
O
O
CO2C2H5
Ph
0102030405060708090100110120130140150160170
14.4
3
61.3
6
76.7
577
.06
77.3
8
102.
64
114.
9112
0.36
120.
6412
4.56
127.
2112
7.57
128.
1312
8.97
129.
29
137.
5314
0.52
142.
5414
2.64
164.
54
13
C-NMR Spectrum of compound 3d
HRMS Spectrum of compound 3d
O
O
CO2C2H5
Ph
O
O
CO2C2H5
Ph
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.05
3.16
2.14
2.15
1.04
1.06
0.99
1.00
0.00
1.42
1.44
1.46
3.90
4.42
4.44
4.46
4.48
6.24
7.13
7.13
7.18
7.18
7.20
7.21
7.26
7.70
7.72
7.95
1H-NMR Spectrum of compound 3e
0102030405060708090100110120130140150160170
14.4
2
55.3
1
61.2
4
76.8
077
.05
77.3
1
102.
35
106.
49
114.
7011
7.34
121.
3112
1.96
122.
13
130.
09
141.
1314
2.84
156.
76
164.
71
13C-NMR Spectrum of compound 3e
O
O
CO2C2H5
H3CO
O
O
CO2C2H5
H3CO
HRMS Spectrum of compound 3e
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.03
3.09
2.02
2.01
2.01
1.01
1.00
0.00
1.42
1.43
1.45
3.93
4.42
4.44
4.45
4.46
6.26
7.00
7.00
7.02
7.02
7.26
7.73
7.75
8.02
1H NMR Spectrum of compound 3f
O
O
CO2C2H5
H3CO
CO2C2H5
H3COO
O
0102030405060708090100110120130140150160170
14.4
0
55.4
4
61.1
0
96.9
7
102.
28
111.
97
118.
6412
2.94
124.
2412
4.67
131.
23
141.
4914
2.98
159.
69
164.
67
13C NMR Spectrum of compound 3f
HRMS Spectrum of compound 3f
CO2C2H5
H3COO
O
CO2C2H5
H3COO
O
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.10
3.07
2.06
2.08
1.02
1.01
0.99
1.00
0.00
1.42
1.44
1.46
2.47
4.42
4.44
4.46
4.48
6.26
7.26
7.33
7.34
7.36
7.36
7.62
7.69
7.71
7.99
1
H-NMR Spectrum of compound 3g
0102030405060708090100110120130140150160170
14.4
1
21.6
7
61.2
3
76.8
077
.06
77.3
1
102.
39
114.
45
119.
5611
9.98
123.
33
128.
1212
9.30
130.
7113
4.34
141.
8714
2.47
164.
70
13
C-NMR Spectrum of compound 3g
O
O
CO2C2H5
H3C
O
O
CO2C2H5
H3C
HRMS Spectrum of compound 3g
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5
f1 (ppm)
SAI-M0009
3.03
3.05
2.01
2.02
2.00
1.01
1.00
-0.0
8
1.34
1.36
1.38
2.68
4.35
4.36
4.38
4.40
6.13
7.09
7.11
7.12
7.12
7.13
7.18
7.54
7.55
7.57
7.95
1H-NMR Spectrum of compound 3h
O
O
CO2C2H5
H3C
OO
CO2C2H5
CH3
0102030405060708090100110120130140150160170180f1 (ppm)
SAI-M0009
14.2
4
24.4
6
60.9
163
.46
63.9
0
76.7
577
.00
77.2
5
120.
7012
4.37
124.
5412
6.86
127.
1112
8.91
130.
3713
3.54
138.
2014
0.13
165.
48
13C-NMR Spectrum of compound 3h
OO
CO2C2H5
CH3
OO
CO2C2H5
CH3
HRMS Spectrum of compound 3h
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.16
2.16
4.21
1.04
1.06
1.04
1.00
1.02
0.00
1.41
1.43
1.45
4.39
4.41
4.43
4.44
4.44
4.45
4.45
4.48
4.48
4.49
4.49
4.49
4.50
7.26
7.37
7.37
7.39
7.39
7.39
7.41
7.41
7.50
7.50
7.51
7.52
7.52
7.53
7.54
7.77
7.80
7.95
8.03
8.03
8.05
1H-NMR Spectrum of compound 4a
0102030405060708090100110120130140150160170180190
14.3
8
61.1
264
.27
64.5
5
76.6
477
.07
77.4
9
120.
3212
1.19
124.
1312
4.90
127.
2912
7.63
128.
61
137.
4613
7.87
165.
65
13C-NMR Spectrum of compound 4a
CO2C2H5
O
O
CO2C2H5
O
O
HRMS Spectrum of compound 4a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
3.12
6.46
1.02
1.00
1.00
0.99
1.40
1.42
1.44
4.39
4.41
4.43
4.44
4.47
4.48
7.55
7.57
7.83
7.90
7.92
7.94
1H-NMR Spectrum of compound 4b
CO2C2H5
O
O
Br
CO2C2H5
O
O
0102030405060708090100110120130140150160170
14.3
6
61.3
364
.29
64.5
3
76.7
577
.07
77.3
9
118.
7912
2.32
122.
9012
5.63
128.
6813
0.39
130.
79
137.
7413
8.19
165.
30
1
3C-NMR Spectrum of compound 4b
HRMS Spectrum of compound 4b
CO2C2H5
O
O
Br
CO2C2H5
O
O
Br
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.08
2.21
2.06
2.16
0.99
1.00
1.00
1.02
0.00
1.41
1.42
1.44
4.40
4.41
4.43
4.43
4.43
4.44
4.44
4.47
4.47
4.48
4.48
7.26
7.43
7.43
7.44
7.45
7.76
7.76
7.83
7.97
7.98
1H-NMR Spectrum of compound 4c
0102030405060708090100110120130140150160170
14.3
5
61.3
164
.31
64.5
2
76.7
577
.06
77.3
8
122.
2312
2.43
122.
8912
5.41
127.
0912
8.22
128.
3413
0.73
137.
7113
8.10
165.
33
13C-NMR Spectrum of compound 4c
CO2C2H5
O
O
Cl
CO2C2H5
O
O
Cl
HRMS Spectrum of Compound 4c
CO2C2H5
O
O
Cl
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.13
2.11
2.31
2.14
1.04
2.15
2.11
1.04
1.02
1.00
1.02
0.00
1.42
1.44
1.46
4.41
4.42
4.44
4.45
4.45
4.45
4.46
4.46
4.47
4.49
4.50
4.50
4.51
4.51
7.26
7.36
7.37
7.39
7.46
7.48
7.50
7.68
7.68
7.70
7.71
7.78
7.78
7.80
7.80
7.99
7.99
8.01
8.10
8.12
1H-NMR Spectrum of compound 4d
0102030405060708090100110120130140150160170
14.4
0
61.1
864
.33
64.6
1
76.7
577
.07
77.3
9
121.
0012
1.61
124.
4312
6.41
127.
2512
7.35
127.
4412
7.94
128.
9213
7.54
137.
6513
8.04
140.
68
165.
62
13C-NMR Spectrum of compound 4d
CO2C2H5
O
O
Ph
CO2C2H5
O
O
Ph
HRMS Spectrum of compound 4d
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.24
3.13
4.48
2.14
1.07
1.03
1.02
1.00
1.41
1.42
1.44
3.89
4.39
4.41
4.42
4.42
4.43
4.45
4.46
4.46
4.46
4.47
7.08
7.09
7.17
7.18
7.19
7.19
7.26
7.84
7.94
7.95
1H-NMR Spectrum of compound 4e
CO2C2H5
O
O
H3CO
CO2C2H5
O
O
Ph
0102030405060708090100110120130140150160170
14.1
514
.39
55.3
3
61.0
764
.40
64.4
5
76.8
077
.05
77.3
0
106.
43
120.
4412
1.53
122.
0112
2.58
128.
78
136.
5613
7.88
157.
02
165.
75
13C-NMR Spectrum of compound 4e
HRMS Spectrum of compound 4e
CO2C2H5
O
O
H3CO
CO2C2H5
O
O
H3CO
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
3.05
3.07
2.04
2.04
2.17
1.00
1.02
1.02
1.00
0.00
1.41
1.42
1.43
3.94
4.38
4.40
4.41
4.42
4.44
4.44
4.45
4.47
4.48
4.49
7.02
7.03
7.04
7.05
7.26
7.29
7.29
7.67
7.69
7.93
1H NMR Spectrum of compound 4f
0102030405060708090100110120130140150160170180
14.3
5
55.3
4
60.8
864
.14
64.5
3
76.7
577
.00
77.2
5
98.3
6
117.
9111
8.20
122.
8612
4.33
128.
7213
0.36
136.
4713
8.69
159.
46
165.
56
13C NMR Spectrum of compound 4f
CO2C2H5
H3COO
O
HRMS Spectrum of compound 4f
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.21
3.24
4.22
2.13
1.04
1.05
1.00
1.02
1.41
1.42
1.44
2.48
4.39
4.41
4.42
4.43
4.43
4.46
4.47
4.47
4.48
7.26
7.34
7.35
7.36
7.36
7.55
7.86
7.92
7.94
1H-NMR Spectrum of compound 4g
CO2C2H5
O
O
H3C
CO2C2H5
H3COO
O
0102030405060708090100110120130140150160170
14.3
9
21.4
9
61.0
764
.31
64.5
2
76.8
077
.06
77.3
1
120.
2112
1.11
123.
4912
5.51
127.
5212
7.91
129.
9813
4.47
137.
2913
7.53
165.
78
13C-NMR Spectrum of compound 4g
CO2C2H5
O
O
H3C
HRMS Spectrum of Compound 4g
CO2C2H5
O
O
H3C
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
SAI M0009
3.05
3.04
4.14
2.04
2.02
1.02
1.00
0.00
1.39
1.41
1.43
2.83
4.38
4.39
4.41
4.44
7.18
7.20
7.25
7.54
7.56
7.58
7.87
1H-NMR Spectrum of compound 4h
0102030405060708090100110120130140150160170180190f1 (ppm)
SAI-M0009
14.2
4
24.4
6
60.9
163
.46
63.9
0
76.7
577
.00
77.2
5
120.
7012
4.37
124.
5412
6.86
127.
1112
8.91
130.
3713
3.54
138.
2014
0.13
165.
48
13C-NMR Spectrum of compound 4h
CO2C2H5
CH3 OO
CO2C2H5
CH3 OO
HRMS Spectrum of compound 4h
CO2C2H5
CH3 OO
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0
3.18
3.16
1.07
4.31
1.05
1.11
1.05
1.00
1.00
0.00
1.41
1.43
1.45
1.47
1.48
4.02
4.03
4.05
4.05
4.07
4.07
4.39
4.40
4.40
4.41
4.41
4.42
4.42
4.43
4.43
4.44
4.44
4.45
4.46
4.47
7.26
7.36
7.36
7.38
7.38
7.38
7.40
7.40
7.49
7.49
7.51
7.51
7.51
7.53
7.53
7.77
7.79
7.95
8.03
8.03
8.05
8.05
1H-NMR Spectrum of compound 4i
0102030405060708090100110120130140150160170180190
14.3
216
.50
61.0
2
68.8
869
.46
120.
3112
1.30
124.
0912
4.71
127.
0412
7.49
128.
56
136.
8613
7.60
165.
83
13C-NMR Spectrum of compound 4i
CO2C2H5
OO
CH3
CO2C2H5
OO
CH3
HRMS Spectrum of Compound 4i
CO2C2H5
OO
CH3
CO2C2H5
OO
CH3
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.30
3.27
1.13
4.11
1.07
1.15
1.05
1.00
1.00
0.00
1.41
1.43
1.45
1.49
1.51
3.93
3.95
3.96
3.98
3.98
4.39
4.41
4.43
4.44
4.44
4.45
4.46
4.47
4.47
4.49
7.26
7.26
7.26
7.26
7.37
7.37
7.39
7.39
7.39
7.41
7.41
7.49
7.50
7.51
7.51
7.52
7.53
7.53
7.78
7.80
7.95
8.07
8.07
8.09
8.09
1H-NMR Spectrum of compound 4ia
0102030405060708090100110120130140150160170180
14.3
516
.69
61.0
7
69.2
7
120.
3712
0.91
123.
9112
4.82
127.
2512
7.48
127.
6512
8.55
137.
33
165.
68
13C-NMR Spectrum of compound 4ia
CO2C2H5
OO
CH3
CO2C2H5
OO
CH3
HRMS Spectrum of Compound 4ia
CO2C2H5
OO
CH3
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5
3.12
2.18
2.11
4.13
1.05
1.08
1.02
1.00
1.00
0.00
1.41
1.43
1.44
2.31
2.33
2.34
4.32
4.34
4.35
4.39
4.39
4.40
4.41
4.41
4.43
4.45
7.26
7.41
7.41
7.43
7.43
7.44
7.45
7.45
7.51
7.51
7.53
7.53
7.53
7.55
7.55
7.80
7.82
7.92
8.16
8.16
8.18
8.18
8.18
1H-NMR Spectrum of compound 5a
0102030405060708090100110120130140150160170180
14.3
3
31.8
2
61.1
4
71.0
071
.10
76.6
877
.00
77.3
2
121.
6012
5.04
125.
5412
7.50
128.
2812
9.31
129.
79
145.
2114
6.57
166.
52
13C-NMR Spectrum of compound 5a
CO2C2H5
O
O
CO2C2H5
O
O
HRMS Spectrum of compound 5a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.17
2.21
2.07
4.31
1.01
1.00
1.02
1.05
1.41
1.42
1.44
2.31
2.32
2.33
2.34
2.35
4.33
4.34
4.35
4.39
4.39
4.40
4.41
4.41
4.42
4.44
7.26
7.56
7.57
7.58
7.58
7.78
7.95
7.95
8.02
8.04
1H-NMR Spectrum of compound 5b
CO2C2H5
O
O
Br
CO2C2H5
O
O
0102030405060708090100110120130140150160170
14.3
5
31.6
6
61.3
6
71.0
571
.22
76.8
077
.05
77.3
1
119.
6412
3.66
123.
7512
6.95
128.
2413
0.11
130.
3813
0.75
145.
3714
6.69
166.
20
13C-NMR Spectrum of compound 5b
HRMS Spectrum of compound 5b
CO2C2H5
O
O
Br
CO2C2H5
O
O
Br
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.12
2.08
3.15
2.09
2.08
2.08
1.03
1.04
1.00
1.00
1.40
1.42
1.43
2.27
2.28
2.30
2.31
2.32
2.47
7.25
7.34
7.34
7.36
7.36
7.56
7.82
8.04
8.06
1H-NMR Spectrum of compound 5c
0102030405060708090100110120130140150160170
14.3
9
21.5
1
32.0
1
61.1
4
71.0
571
.17
76.8
577
.10
77.3
6
121.
5612
4.46
125.
5912
7.27
128.
0512
9.70
129.
91
135.
28
144.
6914
6.78
166.
72
13C-NMR Spectrum of compound 5c
CO2C2H5
O
O
H3C
CO2C2H5
O
O
H3C
HRMS Spectrum of compound 5c
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
3.04
4.34
4.15
2.08
1.01
1.02
1.01
1.00
1.00
0.00
1.41
1.42
1.44
1.92
1.93
1.94
1.94
1.95
1.97
1.98
1.99
2.01
2.01
2.02
2.02
4.39
4.41
4.43
4.43
4.44
4.46
4.56
4.57
4.59
7.25
7.39
7.39
7.41
7.41
7.41
7.43
7.43
7.49
7.49
7.51
7.51
7.51
7.53
7.53
7.78
7.80
7.94
8.13
8.13
8.15
1H-NMR Spectrum of compound 6a
CO2C2H5
O
O
CO2C2H5
O
O
H3C
0102030405060708090100110120130140150160170180
14.2
9
26.5
328
.05
61.0
6
72.0
874
.00
76.7
577
.00
77.2
5
121.
7712
5.05
125.
4112
5.97
127.
3312
8.40
129.
4612
9.98
142.
7914
5.12
166.
49
13C-NMR Spectrum of compound 6a
HRMS Spectrum of compound 6a
CO2C2H5
O
O
CO2C2H5
O
O
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
3.07
2.12
2.16
4.19
2.09
1.00
1.01
1.00
1.02
0.00
1.41
1.42
1.44
1.94
1.94
1.95
1.95
1.97
1.98
2.00
2.02
2.03
2.04
2.05
4.39
4.41
4.43
4.43
4.44
4.46
4.58
4.59
4.60
7.26
7.55
7.56
7.57
7.58
7.80
7.95
7.95
8.01
8.03
1H-NMR Spectrum of compound 6b
0102030405060708090100110120130140150160170180
-0.0
1
14.3
0
26.3
228
.04
61.3
2
72.0
974
.07
76.6
877
.00
77.3
2
119.
5112
3.59
123.
8512
7.42
128.
3813
0.18
130.
54
142.
7514
5.39
166.
24
13C-NMR Spectrum of compound 6b
CO2C2H5
Br
O
O
CO2C2H5
Br
O
O
HRMS Spectrum of compound 6b
CO2C2H5
Br
O
O
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.20
2.28
2.37
3.18
4.32
2.16
1.04
1.05
1.00
1.02
1.41
1.42
1.44
1.93
1.93
1.94
2.00
2.01
2.01
2.02
2.48
4.39
4.41
4.41
4.42
4.43
4.43
4.56
4.57
4.58
7.26
7.34
7.35
7.36
7.37
7.57
7.87
8.03
8.05
1H-NMR Spectrum of compound 6c
102030405060708090100110120130140150160170
14.3
8
21.4
9
26.5
228
.30
61.1
1
72.0
874
.23
76.7
677
.08
77.4
0
121.
8112
4.54
126.
0312
7.43
128.
2012
9.77
129.
90
135.
18
142.
12
145.
49
166.
70
13C-NMR Spectrum of compound 6c
CO2C2H5
H3C
O
O
CO2C2H5
H3C
O
O
HRMS Spectrum of compound 6c
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.26
3.54
3.22
1.14
1.12
2.24
2.24
2.21
1.08
1.12
2.09
1.00
0.00
1.20
1.21
1.23
1.28
1.30
1.31
1.41
1.42
1.43
3.39
3.43
3.51
3.54
4.16
4.17
4.19
4.20
4.29
4.31
4.32
4.34
4.41
4.42
4.44
4.45
7.26
7.36
7.37
7.39
7.50
7.52
7.52
7.54
7.85
7.87
8.11
1H-NMR Spectrum of compound 8a
O
O
CO2C2H5
CO2C2H5CO2C2H5
CO2C2H5
H3C
O
O
0102030405060708090100110120130140150160170
13.9
614
.02
14.3
2
41.0
4
61.2
461
.26
62.7
2
76.8
177
.07
77.3
2
111.
74
114.
59
119.
9612
1.42
124.
7512
5.02
128.
3412
9.13
129.
39
141.
4514
1.79
164.
2416
5.23
167.
37
13C-NMR Spectrum of compound 8a
O
O
CO2C2H5
CO2C2H5CO2C2H5
O
O
CO2C2H5
CO2C2H5CO2C2H5
HRMS Spectrum of Compound 8a
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.11
3.29
3.04
2.10
2.12
2.04
2.09
1.01
1.04
0.94
1.00
0.00
1.19
1.21
1.22
1.28
1.30
1.31
1.40
1.41
1.43
3.39
3.42
3.52
3.55
4.16
4.17
4.19
4.20
4.29
4.31
4.32
4.33
4.41
4.42
4.42
4.43
4.44
4.45
7.27
7.56
7.58
7.58
7.73
7.75
8.01
8.02
8.02
1H-NMR Spectrum of compound 8b
O
O
CO2C2H5
CO2C2H5CO2C2H5
Br
0102030405060708090100110120130140150160170
13.8
913
.96
14.2
3
40.8
7
61.2
461
.40
62.7
7
76.7
577
.00
77.2
5
111.
9711
5.47
118.
7711
9.54
121.
6712
3.62
129.
9513
1.10
131.
55
141.
9114
2.17
163.
7916
4.93
167.
18
13C-NMR Spectrum of compound 8b
O
O
CO2C2H5
CO2C2H5CO2C2H5
Br
O
O
CO2C2H5
CO2C2H5CO2C2H5
Br
HRMS Spectrum of Compound 8b
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.02
3.39
2.98
1.00
0.98
2.05
2.02
1.93
1.00
0.95
0.95
1.00
1.20
1.21
1.23
1.28
1.30
1.31
1.40
1.42
1.43
3.39
3.42
3.52
3.55
4.16
4.17
4.19
4.20
4.29
4.31
4.32
4.34
4.41
4.42
4.44
4.44
4.45
7.27
7.44
7.44
7.45
7.46
7.80
7.82
7.83
7.84
8.01
1H-NMR Spectrum of compound 8c
O
O
CO2C2H5
CO2C2H5CO2C2H5
Cl
0102030405060708090100110120130140150160170
13.9
414
.02
14.1
414
.28
40.9
3
61.2
861
.43
62.8
1
76.7
477
.06
77.3
8
112.
0011
5.60
119.
4412
1.70
123.
6612
7.82
129.
2412
9.56
130.
81
141.
8714
2.19
163.
8716
4.99
167.
22
13C-NMR Spectrum of compound 8c
O
O
CO2C2H5
CO2C2H5CO2C2H5
Cl
O
O
CO2C2H5
CO2C2H5CO2C2H5
Cl
HRMS Spectrum of Compound 8c
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0
3.14
3.02
3.19
2.11
2.12
2.10
2.03
1.09
2.19
2.08
1.05
1.02
1.01
1.00
0.00
1.21
1.22
1.24
1.25
1.29
1.31
1.33
1.41
1.43
1.45
3.40
3.44
3.53
3.57
4.17
4.18
4.20
4.22
4.30
4.32
4.33
4.35
4.41
4.43
4.45
4.47
7.26
7.26
7.39
7.41
7.47
7.49
7.51
7.67
7.68
7.69
7.70
7.79
7.79
7.81
7.82
7.93
7.95
8.05
8.06
8.06
8.17
1H-NMR Spectrum of compound 8d
O
O
CO2C2H5
CO2C2H5CO2C2H5
Ph
0102030405060708090100110120130140150160170
13.9
314
.00
14.2
9
40.9
9
61.2
261
.27
62.7
1
76.7
577
.00
77.2
5
111.
80
114.
9512
0.56
125.
0212
7.05
127.
2112
7.59
128.
2312
8.94
129.
45
137.
7714
0.44
141.
5914
1.85
164.
1716
5.17
167.
33
13C-NMR Spectrum of compound 8d
HRMS Spectrum of compound 8d
O
O
CO2C2H5
CO2C2H5CO2C2H5
Ph
O
O
CO2C2H5
CO2C2H5CO2C2H5
Ph
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5
3.26
3.54
3.11
1.09
1.10
3.15
2.21
2.47
2.15
1.05
1.01
1.03
1.00
0.00
1.20
1.21
1.23
1.26
1.28
1.30
1.31
1.40
1.41
1.43
3.37
3.40
3.50
3.53
3.90
4.16
4.17
4.19
4.20
4.29
4.29
4.30
4.31
4.32
4.33
4.40
4.41
4.43
4.44
7.13
7.13
7.19
7.19
7.21
7.21
7.26
7.76
7.78
7.97
1H-NMR Spectrum of compound 8e
0102030405060708090100110120130140150160170
13.9
514
.02
14.3
2
41.0
4
55.3
4
61.2
062
.67
76.7
277
.04
77.3
6
106.
48
111.
5611
4.79
117.
10
121.
5412
2.02
122.
67
130.
34
140.
1414
2.16
156.
95
164.
3816
5.30
167.
41
13C-NMR Spectrum of compound 8e
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3CO
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3CO
HRMS Spectrum of compound 8e
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0
3.32
3.71
3.11
3.15
1.08
1.05
2.17
2.17
2.10
1.11
1.05
1.04
1.00
1.19
1.21
1.23
1.28
1.29
1.31
1.40
1.41
1.43
2.47
3.38
3.42
3.50
3.54
4.15
4.17
4.19
4.21
4.28
4.30
4.32
4.33
4.39
4.41
4.43
4.45
7.26
7.35
7.35
7.37
7.37
7.62
7.75
7.78
8.01
1H-NMR Spectrum of compound 8f
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3C
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3CO
0102030405060708090100110120130140150160170
13.9
514
.01
14.3
1
21.6
7
41.0
6
61.1
962
.66
76.7
677
.07
77.3
9
111.
60
114.
52
119.
7912
3.86
128.
0312
9.49
130.
8213
4.64
140.
8614
1.79
164.
3716
5.31
167.
42
13C-NMR Spectrum of compound 8f
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3C
O
O
CO2C2H5
CO2C2H5CO2C2H5
H3C
HRMS Spectrum of Compound 8f