Organic & Biomolecular Chemistry
DOI: 10.1039/C8OB03123A
quenched by adding water (50 mL), and extracted with EtOAc (3 x 30 mL). The combined organic
layers were dried over Na SO , concentrated under reduced pressure and the crude was purified
2
4
on silica gel column chromatography (Hexane/EtOAc, 1:1) to give product 10 as yellow oil (2.53
1
g, 82% yield); H NMR (400 MHz, CDCl ) δ 7.53 – 7.19 (m, 5H), 7.14 (t, J = 7.7 Hz, 1H), 6.89
3
(t, J = 15.9 Hz, 1H), 6.84 – 6.54 (m, 1H), 5.00 (d, J = 11.8 Hz, 2H), 4.70 (d, J = 51.2 Hz, 1H), 3.92
1
3
(
s, 3H), 3.12 – 2.77 (m, 2H), 2.35 – 1.93 (m, 9H); C NMR (100 MHz, CDCl ) δ 206.6, 178.7,
3
1
56.0, 144.2, 141.2, 136.4, 129.8, 128.5, 128.1, 128.0, 125.5, 115.1, 112.9, 66.6, 56.2, 49.9, 38.0,
3
7.6, 37.2, 32.0, 29.9; IR (neat): υmax 3341, 2019, 2928, 2853, 1802, 1713, 1604, 1512, 1455, 1257,
-1
+
1
170, 1034, 883, 844, 767, 701 cm ; HRMS (ESI) calcd for C H NO Na [M+Na] : 434.1580;
23 25 6
found: 434.1568.
Benzyl 7-methoxy-5-oxo-4a-(3-oxobutyl)-3,4,4a,5-tetrahydrobenzofuro[4,3-cd]azepine-2(1-
H)-carboxylate (11):
To a solution of 10 (2.3 g, 5.59 mmol, 1.0 equiv) in 1,2-dichloroethane (30 mL) were added
paraformaldehyde (0.83 g, 27.98 mmol, 5.0 equiv) and TFA (4.28 mL, 55.96 mmol, 10.0 equiv)
at room temperature. The mixture was stirred at 60 °C for 12 h, quenched with saturated aqueous
NaHCO at 0 °C and extracted with CH Cl (3 x 30 mL). The organics were combined and dried
3
2
2
over Na SO . After filtration, the solvent was concentrated under reduced pressure and the crude
2
4
was purified on silica gel column chromatography (Hexane/EtOAc, 3:2) which afforded 11 as a
1
yellow oil (2.44 g, 95% yield) in 1:1 ratio of isomers; H NMR (500 MHz, CDCl ) δ 7.38 – 7.26
3
(m, 3.5H), 7.26 – 7.17 (m, 1.5H), 7.04 (d, J = 8.4 Hz, 0.5H), 6.82 (d, J = 8.0 Hz, 0.5H), 6.80 (d, J
=
7.4 Hz, 0.5H), 6.72 (d, J = 8.4 Hz, 0.5H), 5.11 (d, J = 12.3 Hz, 0.5H), 5.01 (td, J = 12.4, 7.7 Hz,
1
1
0
2
1
1
3
1
H), 4.97 – 4.89 (m, 0.5H), 4.80 (d, J = 15.3 Hz, 0.5H), 4.67 (d, J = 15.6 Hz, 0.5H), 4.43 (d, J =
4.8 Hz, 0.5H), 4.32 (d, J = 15.2 Hz, 0.5H), 4.23 (d, J = 15.6 Hz, 0.5H), 4.15 (d, J = 15.2 Hz,
.5H), 3.93 (s, 1.5H), 3.92 (s, 1.5H), 3.55 (ddd, J = 26.8, 20.2, 7.5 Hz, 1H), 2.74 – 2.63 (m, 1H),
1
3
.46 – 2.33 (m, 1H), 2.19 – 1.83 (m, 7H); C NMR (125 MHz, CDCl ) δ 206.4, 178.3, 178.1,
3
55.3, 155.2, 143.4, 140.8, 140.8, 136.5, 129.5, 129.1, 128.5, 128.4, 128.1, 128.0, 127.9, 127.8,
24.8, 124.3, 112.3, 112.0, 67.4, 67.3, 56.4, 56.3, 50.8, 50.3, 50.2, 45.6, 45.2, 37.7, 33.4, 32.4,
0.1, 27.8, 27.6; IR (neat): υmax 3506, 3542, 2950, 1803, 1701, 1635, 1599, 1512, 1427, 1363,
-1
281, 1231, 1171, 1138, 1068, 1013, 920, 817, 738, 700 cm ; HRMS (ESI) calcd for
+
C H NO Na [M+Na] : 446.1580; found: 446.1573.
2
4
25
6
1
0