Page 9 of 24
The Journal of Organic Chemistry
5.41–5.36 (m, 1H), 3.70 (s, 2H), 2.74 (d, J = 5.2 Hz, 1H), 2.74
1242, 1117, 1069, 1027, 765, 694; HRLCMS-ESI (m/z) Calcd
for (C20H23N2O2) ([M+H]+): 323.1754; found: 323.1762.
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5
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(d, J = 6.9 Hz, 1H), 2.43 (s, 3H), 1.53 (s, 3H), 1.49 (s, 3H);
13C{1H} NMR (CDCl3, 125 MHz): δ 147.3, 140.5, 138.8, 129.1,
128.1, 127.6, 127.1, 126.8, 121.7, 120.4, 85.2, 79.4, 63.8, 62.9,
43.0, 30.0, 29.1; FTIR (thin film): cm-1 2969, 2790, 1454, 1360,
1154, 1024, 759, 737, 698; HRLCMS-ESI (m/z) Calcd for
(C19H24NO) ([M+H]+): 282.1852; found: 282.1855.
(Z)-3-(Morpholinomethyl)-N-phenylisobenzofuran-1(3H)-
imine (5c). Synthesized using standard conditions. Isolated by
flash column chromatography (5% EtOAc–hexanes to 50%
EtOAc–hexanes) as a yellow oil (43.2 mg, 35%). Rf = 0.30 (5%
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MeOH–CH2Cl2); H NMR (CDCl3, 400 MHz): δ 7.96 (d, J =
7
8
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N-((3,3-Dimethyl-1,3-dihydroisobenzofuran-1-yl)methyl)-
N-methyl-2-phenylethan-1-amine (3af). Synthesized using
standard conditions. Isolated by flash column chromatography
(addition of 0.2 mL TFA to crude reaction mixture, 50%
EtOAc–hexanes, then 50% EtOAc–hexanes with 5% NEt3) as
an orange oil (84.9 mg, 72%). Rf = 0.20 (5% MeOH–CH2Cl2);
1H NMR (CDCl3, 400 MHz): δ 7.34–7.12 (m, 9H), 5.35 (t, J =
6.0 Hz, 1H), 2.92–2.76 (m, 6H), 2.53 (s, 3H), 1.60 (s, 3H), 1.51
(s, 3H); 13C{1H} NMR (CDCl3, 125 MHz): δ 147.3, 140.5,
140.4, 128.6, 128.2, 127.6, 127.1, 125.8, 121.6, 120.4, 85.1,
79.2, 64.2, 60.2, 42.9, 33.4, 30.0, 29.0; FTIR (thin film): cm-1
2969, 2793, 1453, 1359, 1028, 745, 698; HRLCMS-ESI (m/z)
Calcd for (C20H26NO) ([M+H]+): 296.2009; found: 296.2013.
7.4 Hz, 1H), 7.59–7.46 (m, 3H), 7.37–7.27 (m, 4H), 7.10 (tt, J
= 7.1, 1.6 Hz, 1H), 5.63 (dd, J = 6.8, 4.8 Hz, 1H), 3.70 (dt, J =
5.9, 3.6 Hz, 4H), 2.86 (dd, J = 13.6, 4.8 Hz, 1H), 2.74 (dd, J =
13.6, 6.8 Hz, 1H), 2.68 (ddd, J = 11.6, 5.8, 3.6 Hz, 2H), 2.51
(ddd, J = 11.6, 5.8, 3.6 Hz, 2H); 13C{1H} NMR (CDCl3, 125
MHz): δ 158.2, 146.5, 145.3, 131.8, 130.9, 129.0, 128.5, 123.9,
123.9, 123.3, 121.8, 82.5, 67.0, 62.8, 54.2; FTIR (thin film):
cm-1 2852, 2811, 1681, 1593, 1488, 1294, 1199, 1116, 1070,
1009, 866, 753, 695; HRLCMS-ESI (m/z) Calcd for
(C19H21N2O2) ([M+H]+): 309.1598; found: 309.1602.
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(5-Methyl-5-(morpholinomethyl)-2-phenyl-4,5-
dihydrofuran-3-yl)(phenyl)methanone (5e). Synthesized
using standard conditions. Isolated by flash column
chromatography (100% hexanes to 30% EtOAc–hexanes) as a
4-(Morpholinomethyl)-2-phenyl-4H-benzo[d][1,3]oxazine
(5a). Synthesized using standard conditions. Isolated by flash
column chromatography (100% Hexanes to 40% EtOAc–
hexanes) as an off-white solid (64.0 mg, 52%). Rf = 0.35 (5%
MeOH–CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ 8.20–8.14 (m,
2H), 7.53–7.42 (m, 3H), 7.35–7.28 (m, 2H), 7.18 (ddd, J = 7.5,
5.9, 2.9 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 5.56 (dd, J = 7.9, 4.3
Hz, 1H), 3.71 (t, J = 4.6 Hz, 4H), 2.91 (dd, J = 13.8, 7.9 Hz,
1H), 2.65 (dd, J = 13.8, 4.3 Hz, 1H), 2.56 (t, J = 4.6 Hz, 4H);
13C{1H} NMR (CDCl3, 125 MHz): δ 156.6, 139.3, 132.7, 131.4,
129.0, 128.2, 128.0, 126.3, 124.9, 124.6, 124.4, 74.3, 67.1, 63.5,
54.1; FTIR (thin film): cm-1 2956, 2852, 2809, 1623, 1598,
1573, 1483, 1450, 1261, 1116, 1081, 1070, 764, 694;
HRLCMS-ESI (m/z) Calcd for (C19H21N2O2) ([M+H]+):
309.1598; found: 309.1603.
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clear oil (44.6 mg, 31%). Rf = 0.30 (5% MeOH–CH2Cl2); H
NMR (CDCl3, 400 MHz): δ 7.42 (d, J = 7.8 Hz, 2H), 7.20 (t, J
= 7.4 Hz, 1H), 7.17–7.12 (m, 3H), 7.09–7.00 (m, 4H), 3.71 (t, J
= 4.6 Hz, 4H), 3.35 (d, J = 14.8 Hz, 1H), 2.96 (d, J = 14.8 Hz,
1H), 2.70–2.62 (m, 4H), 2.59 (ddd, J = 11.6, 4.6 Hz, 2H), 1.55
(s, 3H); 13C{1H} NMR (CDCl3, 125 MHz): δ 193.7, 164.7,
139.2, 130.9, 130.4, 129.8, 129.1, 128.8, 127.5, 112.0, 88.8,
67.1, 66.2, 55.1, 42.6, 24.8; FTIR (thin film): cm-1 2925, 2852,
1611, 1592, 1573, 1491, 1446, 1367, 1272, 1249, 1117, 1069,
893, 865, 695; HRLCMS-ESI (m/z) Calcd for (C23H26NO3)
([M+H]+): 364.1907; found: 364.1912.
4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)morpholine
(5f). Synthesized using standard conditions with the following
modification: with copper(II) acetate instead of copper(II)
trifluoromethanesulfonate and 1,2-dimethoxyethane instead of
1,2-dichloroethane. Isolated by flash column chromatography
(100% hexanes to 70% EtOAc–hexanes) as a clear oil (49.1 mg,
4-(1-Morpholinoethyl)-2-phenyl-4H-benzo[d][1,3]oxazine
(5b). Synthesized using standard conditions. Two
diastereomers of 5b were observed in the crude mixture in a
ratio of 3.3:1 by 1H NMR. Isolated by flash column
chromatography (100% Hexanes to 25% EtOAc–hexanes) to
yield 5b (77.7 mg, 60%). Major diastereomer. Isolated as a
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50%).Rf = 0.23 (5% MeOH–CH2Cl2); H NMR (CDCl3, 400
MHz): δ 7.68–7.64 (m, 2H), 7.41–7.37 (m, 3H), 4.90 (dddd, J
= 10.5, 8.1, 6.5, 5.0 Hz, 1H), 3.69 (t, J = 4.7 Hz, 4H), 3.39 (dd,
J = 16.6, 10.5 Hz, 1H), 3.18 (dd, J = 16.6, 8.1 Hz, 1H), 2.67 (dd,
J = 13.2, 6.5 Hz, 1H), 2.62–2.49 (m, 4H), 2.57 (dd, J = 13.2, 5.0
Hz, 1H); 13C{1H} NMR (CDCl3, 125 MHz): δ 156.4, 129.9,
129.5, 128.6, 126.5, 79.3, 66.8, 62.1, 54.1, 38.7; FTIR (thin
film): cm-1 2853, 1676, 1447, 1356, 1114, 1010, 905, 865, 760,
692; HRLCMS-ESI (m/z) Calcd for (C14H19N2O2) ([M+H]+):
247.1441; found: 247.1443.
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clear oil (60.6 mg, 47%). Rf = 0.27 (5% MeOH–CH2Cl2); H
NMR (CDCl3, 400 MHz): δ 8.17–8.10 (m, 2H), 7.54–7.40 (m,
3H), 7.33–7.24 (m, 2H), 7.18 (td, J = 7.1, 1.8 Hz, 1H), 7.04 (d,
J = 7.4 Hz, 1H), 5.61 (d, J = 4.0 Hz, 1H), 3.75–3.63 (m, 4H),
2.92 (qd, J = 6.8, 4.0 Hz, 1H), 2.71 (ddd, J = 11.2 5.8, 3.3 Hz,
2H), 2.62 (ddd, J = 11.2, 5.8, 3.3 Hz, 2H), 1.11 (d, J = 6.8 Hz,
3H); 13C{1H} NMR (CDCl3, 125 MHz): δ 156.6, 139.1, 132.4,
131.2, 128.6, 128.2, 127.6, 126.0, 125.0, 124.8, 123.9, 77.7,
67.2, 66.0, 50.0, 8.7; FTIR (thin film): cm-1 2958, 2853, 1625,
1598, 1573, 1484, 1449, 1263, 1116, 1068, 1026, 762, 694;
HRLCMS-ESI (m/z) Calcd for (C20H23N2O2) ([M+H]+):
323.1754; found: 323.1762. Minor diastereomer. Isolated as a
white solid (17.1 mg, 13%). Rf = 0.47 (5% MeOH–CH2Cl2); 1H
NMR (CDCl3, 400 MHz): δ 8.30–8.23 (m, 2H), 7.54–7.42 (m,
3H), 7.36–7.29 (m, 2H), 7.17 (td, J = 7.0, 2.2 Hz, 1H), 7.07 (d,
J = 7.8 Hz, 1H), 5.29 (d, J = 7.7 Hz, 1H), 3.68 (t, J = 4.4 Hz,
4H), 3.00–2.90 (m, 1H), 2.69 (dt, J = 11.2, 4.4 Hz, 2H), 2.43
(dt, J = 11.2, 4.4 Hz, 2H), 0.97 (d, J = 6.8 Hz, 3H); 13C NMR
(CDCl3, 125 MHz): δ 157.2, 139.8, 132.7, 131.4, 128.8, 128.4,
128.1, 125.8, 125.6, 124.7, 124.4, 67.4, 61.9, 49.4, 9.3; FTIR
(thin film): cm-1 2953, 2853, 1620, 1596, 1572, 1481, 1449,
3-Methyl-3-(morpholinomethyl)benzo[c]thiophen-1(3H)-
one (5i). Synthesized using standard conditions. Isolated by
flash column chromatography (100% hexanes to 30% EtOAc–
hexanes) as a yellow oil (16.7 mg, 16%). Rf = 0.57 (5%
1
MeOH–CH2Cl2); H NMR (CDCl3, 400 MHz): δ 7.76 (d, J =
7.4 Hz, 1H), 7.59 (td, J = 7.4, 1.4 Hz, 1H), 7.55 (d, J = 7.4 Hz,
1H), 7.44 (td, J = 7.4, 1.4 Hz, 1H), 3.61 (ddd, J = 11.4, 6.1, 3.2
Hz, 2H), 3.56 (ddd, J = 11.4, 6.1, 3.2 Hz, 2H), 2.88 (d, J = 14.1
Hz, 1H), 2.77 (d, J = 14.1 Hz, 1H), 2.55 (ddd, J = 11.4, 6.1, 3.2
Hz, 2H), 2.48 (ddd, J = 11.4, 6.1, 3.2 Hz, 2H), 1.85 (s, 3H);
13C{1H} NMR (CDCl3, 125 MHz): δ 196.6, 154.0, 136.1, 133.0,
128.3, 123.6, 123.5, 68.9, 67.2, 62.1, 55.4, 25.8; FTIR (thin
film): cm–1 2958, 2849, 2806, 1682, 1455, 1116, 1010, 909,
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