The Journal of Organic Chemistry
Page 8 of 12
153.0, 143.6, 136.8, 135.8, 134.7, 129.6, 129.1, 127.6, 121.4, 119.3,
(m, 1H), 7.45 – 7.39 (m, 1H), 7.22 – 7.18 (m, 1H), 4.82 (d, J = 16.3
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118.0, 81.3, 53.6, 52.9, 38.2, 28.6. HRMS (ESI): calcd for
Hz, 1H), 4.55 (d, J = 16.3 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 1.63 (s,
9H), 1.34 (s, 9H), 1.24 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 169.1, 167.6, 149.9, 149.0, 140.5, 132.0, 125.3, 124.2, 123.7,
115.9, 95.8, 85.0, 84.8, 62.2, 61.4, 28.4, 27.8, 14.4. HRMS (ESI):
calcd for C22H29NO9Na [M+Na]+ 474.1740; found 474.1719.
C23H26N2O6Na [M+Na]+ 449.1689; found 449.1699.
Methyl
(2-(2-((Boc)amino)phenyl)-2-oxoacetyl)-L-valinate
(3am). 310 mg (0.820 mmol), 68 % yield. 1H NMR (400 MHz,
CDCl3) δ 10.65 (s, 1H), 8.72 (d, J = 8.6 Hz, 1H), 8.54 (d, J = 8.1
Hz, 1H), 7.84 (t, J = 7.9 Hz, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.29 (t,
J = 7.6 Hz, 1H), 4.93 (dd, J = 8.9, 4.9 Hz, 1H), 4.08 (s, 3H), 2.78
– 2.35 (m, 1H), 1.84 (s, 9H), 1.30 (dd, J = 16.6, 6.8 Hz, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 190.8, 171.3, 163.0, 152.5, 143.1,
136.3, 134.2, 121.0, 118.8, 117.6, 80.8, 57.2, 52.2, 31.2, 28.1, 18.9, 17.6.
HRMS (ESI): calcd for C19H26N2O6Na [M+Na]+ 401.1689; found
401.1674.
7-(tert-butyl) 8-(2-chloroethyl) 8-((tert-butoxycarbonyl)oxy)-
7-azabicicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate (4ae).
Performed on 100 mg of 3ae. 61 mg (0.143 mmol), 47 % yield.
FC performed with a mixture of Petroleum Ether/Diethyl
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Ether as eluant in gradient from 30:1 to 25:1. H NMR (400
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MHz, CDCl3) δ 7.88 (d, J = 8.2 Hz, 1H), 7.46-7.40 (m, 2H), 7.20
(td, J = 7.6, 0.9 Hz, 1H), 4.31 (td, J = 6.1, 1.5 Hz, 2H), 3.63 (td, J
= 6.2, 0.8 Hz, 2H), 1.64 (s, 9H), 1.34 (s, 9H). 13C{1H} NMR (101
MHz, CDCl3) δ 167.3, 149.6, 148.7, 140.0, 131.6, 124.9, 124.1, 123.3,
115.6, 96.0, 84.8, 84.4, 64.5, 42.3, 28.1, 27.4. HRMS (ESI): calcd
for C20H26NO7NaCl [M+Na]+ 450.1295; found 450.1286.
Synthesis of benzoazetidines 4aa-5db. 100 mg of 3 (0.34
mmol, 1 equiv) were dissolved in 1.2 mL of dichloromethane.
The solution was cooled down to 4 °C. After 10 minutes 230
mg of Boc2O (1.06 mmol, 3.1 equiv) were added and the solu-
tion was stirred for 30 minutes at the same temperature. After
that time 6 mg of DMAP (0.051 mmol, 15 mol %) were added
and the mixture was stirred for 1-48 h. The crude was purified
with flash silica chromatography using as eluant a mixture of
hexane/ethyl acetate (30:1 to 5:1).
7-(tert-butyl) 8-(2-iodoethyl) 8-((tert-butoxycarbonyl)oxy)-7-
azabicicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate
(4af).
Performed on 18 mg of 3af. 5 mg (0.00945 mmol), 22 % yield.
FC performed with a mixture of Hexane/Diethyl Ether as elu-
ant in gradient from 20:1 to 10:1. 1H NMR (400 MHz, CDCl3) δ
7.88 (d, J = 8.1 Hz, 1H), 7.50 – 7.38 (m, 2H), 7.21 (t, J = 7.1 Hz,
1H), 4.30 (td, J = 7.1, 1.2 Hz, 2H), 3.24 (t, J = 7.2 Hz, 2H), 1.64 (s,
9H), 1.34 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3) δ 167.7, 150.0,
149.1, 140.3, 131.9, 125.2, 125.1, 123.6, 115.9, 96.2, 85.2, 84.8, 65.5,
28.4, 27.8, 1.8. HRMS (ESI): calcd for C20H26NO7KI [M+K]+
558.0391; found 558.0364.
7-(tert-butyl) 8-methyl 8-((tert-butoxycarbonyl)oxy)-7-azabi-
cicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate (4aa). Per-
formed on 84 mg of 3aa. 52 mg (0.137 mmol), 46 % yield. FC
performed with a mixture of Petroleum Ether/Ethyl Acetate as
eluant in gradient from 20:1 to 5:1. 1H NMR (400 MHz, CDCl3)
δ 7.88 (d, J = 8.1 Hz, 1H), 7.42 (ddd, J = 9.4, 5.8, 1.9 Hz, 2H), 7.19
(td, J = 7.6, 0.9 Hz, 1H), 3.69 (s, 3H), 1.64 (s, 9H), 1.34 (s, 9H).
13C{1H} NMR (101 MHz, CDCl3) δ 167.1, 149.9, 148.8, 140.0, 131.4,
124.7, 124.2, 123.2, 115.6, 96.3, 84.7, 84.1, 52.4, 28.1, 27.4. HRMS
(ESI): calcd for C19H25NO7Na [M+Na]+ 402.1529; found
402.1528.
8-allyl 7-(tert-butyl) 8-((tert-butoxycarbonyl)oxy)-7-azabicicy-
clo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate (4ag). Performed
on 100 mg of 3ag. 47 mg (0.112 mmol), 36 % yield. FC per-
formed with a mixture of Petroleum Ether/Ethyl Acetate as el-
uant in gradient from 20:1 to 8:1. 1H NMR (400 MHz, CDCl3) δ
7.87 (d, J = 8.2 Hz, 1H), 7.45 (d, J = 7.4 Hz, 1H), 7.41 (dd, J = 11.3,
4.5 Hz, 1H), 5.90 (ddt, J = 22.8, 10.9, 5.7 Hz, 1H), 5.28 (dd, J =
17.2, 1.2 Hz, 1H), 5.16 (d, J = 10.4 Hz, 1H), 4.71 – 4.46 (m, 2H),
1.64 (s, 9H), 1.34 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3) δ 167.7,
150.2, 149.2, 140.3, 133.6, 131.7, 125.1, 124.8, 123.6, 118.1, 115.9, 96.5,
85.0, 84.5, 66.1, 28.4, 27.8. HRMS (ESI): calcd for C21H27NO7Na
[M+Na]+ 428.1685; found 428.1665.
7-(tert-butyl) 8-ethyl 8-((tert-butoxycarbonyl)oxy)-7-azabi-
cicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate (4ab). Per-
formed on 77 mg of 3ab. 63 mg (0.160 mmol), 61 % yield. FC
performed with a mixture of Hexane/Ethyl Acetate as eluant
in gradient from 40:1 to 5:1. 1H NMR (400 MHz, CDCl3) δ 7.88
(d, J = 8.2 Hz, 1H), 7.46 – 7.36 (m, 2H), 7.19 (td, J = 7.6, 0.9 Hz,
1H), 4.14 – 4.00 (m, 2H), 1.64 (s, 9H), 1.33 (s, 9H), 1.21 (t, J = 7.1
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 167.8, 150.3, 149.2,
140.3, 131.6, 125.0, 124.9, 123.6, 115.9, 96.8, 85.0, 84.4, 61.0, 28.4,
27.8, 15.5. HRMS (ESI): calcd for C20H27NO7Na [M+Na]+
416.1685; found 416.1666.
8-(but-3-en-2-yl) 7-(tert-butyl) 8-((tert-butoxycarbonyl)oxy)-7-
azabicicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate
(4ah).
Performed on 64 mg of 3ah. 46 mg (0.110 mmol), 54 % yield.
FC performed with a mixture of Petroleum Ether/Ethyl Ace-
tate as eluant in gradient from 20:1 to 7:1. 1H NMR (400 MHz,
CDCl3) δ 7.87 (dd, J = 8.1, 2.7 Hz, 1H), 7.49 – 7.35 (m, 2H), 7.18
(td, J = 7.6, 0.9 Hz, 1H), 5.94 – 5.76 (m, 1H), 5.24 – 4.95 (m, 3H),
1.64 (s, 9H), 1.33 (s, 9H), 1.26 (d, J = 6.4 Hz, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 168.5, 150.3, 149.2, 140.3, 139.6, 131.6, 125.1,
123.7, 123.3, 115.8, 114.9, 96.6, 84.9, 84.2, 72.5, 28.4, 27.8, 21.7.
HRMS (ESI): calcd for C22H29NO7Na [M+Na]+ 442.1842; found
442.1824.
7-(tert-butyl) 8-(2-oxopropyl) 8-((tert-butoxycarbonyl)oxy)-7-
azabicicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarboxylate
(4ac).
Performed on 100 mg of 3ac. 71 mg (0.168 mmol), 54 % yield.
FC performed with a mixture of Hexane/Diethyl Ether as elu-
1
ant in gradient from 20:1 to 1:1. H NMR (400 MHz, CDCl3) δ
7.88 (d, J = 8.2 Hz, 1H), 7.50 – 7.40 (m, 2H), 7.21 (td, J = 7.6, 0.8
Hz, 1H), 4.74 (d, J = 17.1 Hz, 1H), 4.59 (d, J = 17.1 Hz, 1H), 2.16
(s, 3H), 1.63 (s, 9H), 1.34 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3)
δ 204.6, 167.9, 150.0, 149.1, 140.6, 132.2, 125.5, 124.3, 123.8, 116.1,
96.0, 85.4, 85.1, 69.7, 28.5, 27.9, 26.9. HRMS (ESI): calcd for
C21H27NO8Na [M+Na]+ 444.1634; found 444.1625.
Tert-butyl 8-((tert-butoxycarbonyl)(butyl)carbamoyl)-8-((tert-
butoxycarbonyl)oxy)-7-azabicicyclo[4.2.0]octa-1,3,5-triene-
7,8-dicarboxylate (4ai). Performed on 118 mg of 3ai. 53 mg
(0.124 mmol), 34 % yield. FC performed with a mixture of Hex-
7-(tert-butyl) 8-(2-ethoxy-2-oxoethyl) 8-((tert-butoxycar-
bonyl)oxy)-7-azabicicyclo[4.2.0]octa-1,3,5-triene-7,8-dicarbox-
ylate (4ad). Performed on 59 mg of 3ad. 29 mg (0.0643 mmol),
38 % yield. FC performed with a mixture of Petroleum
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ane/Ethyl Acetate as eluant in gradient from 40:1 to 15:1. H
NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.2 Hz, 1H), 7.68 (d, J =
7.4 Hz, 1H), 7.55 (m, 1H), 7.12 (t, J = 7.5 Hz, 1H), 3.68 – 3.62 (m,
2H), 1.69 (m, 2H), 1.59 (s, 9H), 1.45 – 1.35 (m, 2H), 1.32 (s, 9H),
1.09 (s, 9H), 0.97 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 151.4, 150.5, 148.7, 136.4, 123.4, 123.4, 123.2, 116.0, 93.1,
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Ether/Ethyl Acetate as eluant in gradient from 20:1 to 1:1. H
NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.2 Hz, 1H), 7.52 – 7.46
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