W.-J. Huang, C.-I. Chang, et al.
MED
8.3 Hz, 2H), 7.00 (d, J=8.6 Hz, 1H), 6.96 (d, J=8.3 Hz, 2H), 6.21 (s,
1H), 6.13 (d, J=8.6 Hz, 1H), 5.90 (d, J=16.1 Hz, 1H), 4.73 (s, 2H),
3.32 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO): d=164.1, 162.0,
157.9, 136.7, 133.5, 132.0, 130.2, 129.3, 121.6, 117.3, 117.0, 106.8,
100.4, 69.3, 55.9 ppm; HRMS-ESI: m/z [M+H]+ calcd for
C17H17BrNO4: 378.0341, found: 378.0340.
tion of 17c (250 mg, 0.67 mmol) in THF (10 mL) was treated with
ethyl chloroformate (109 mg, 1.00 mmol) and Et3N (0.19 mL,
1.34 mmol) gave 18c (166 mg, 64%) as a white solid: mp: 82–
1
888C; H NMR (500 MHz, [D6]DMSO): d=10.62 (s, 1H), 9.46 (s, 1H),
7.57 (d, J=15.9 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 6.83 (d, J=9.4 Hz,
2H), 6.79 (d, J=9.4 Hz, 2H), 6.56 (s, 1H), 6.52 (d, J=8.4 Hz, 1H),
6.35 (d, J=15.9 Hz, 1H), 4.06 (t, J=5.7 Hz, 2H), 3.93 (t, J=5.7 Hz,
2H), 3.74 (s, 3H), 3.64 (s, 3H), 1.86 ppm (m, 4H); 13C NMR
(125 MHz, [D6]DMSO): d=164.2, 162.1, 158.8, 153.8, 153.1, 134.0,
129.9, 117.2, 116.7, 115.8, 115.1, 106.5, 99.6, 68.3, 68.0, 55.9, 55.8,
26.1, 25.8 ppm; HRMS-ESI: m/z [MÀH]À calcd for C21H24NO6:
386.1604, found: 386.1609.
(E)-N-Hydroxy-2-(4-methoxybenzyloxy)-4-methoxycinnamide
(13d): Following the procedure as described for 13a, reaction of
12d (2.20 g, 7.00 mmol) in THF (40 mL) with ethyl chloroformate
(1.86 mL, 10.51 mmol) and Et3N (2.80 mL, 10.51 mmol) gave 13d
1
(1.04 g, 45%) as a white solid: mp: 145–1508C; H NMR (500 MHz,
[D6]acetone): d=7.98 (d, J=15.8 Hz, 1H), 7.61 (d, J=8.4 Hz, 1H),
7.55 (d, J=8.6 Hz, 2H), 7.07 (d, J=8.6 Hz, 2H), 6.81 (d, J=2.2 Hz,
1H), 6.67 (dd, J=8.6, 2.2 Hz, 1H), 6.64 (d, J=15.8 Hz, 1H), 5.27 (s,
2H), 3.93 (s, 3H), 3.92 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO):
d=162.5, 159.7, 158.6, 135.6, 129.0, 128.8, 116.8, 114.4, 113.6,
105.8, 99.5, 69.9, 54.5, 54.3 ppm; HRMS-ESI: m/z [M+H]+ calcd for
C18H20NO5: 330.1341, found: 330.1341.
(E)-N-Hydroxy-2-(2-(4-methoxyphenoxyoxy)pentyloxy)-4-me-
thoxycinnamide (18d): Following the procedure described for 8a,
reaction of 17d (200 mg, 0.52 mmol) in THF (10 mL) with ethyl
chloroformate (85 mg, 0.78 mmol) and Et3N (0.15 mL, 1.04 mmol)
gave 18d (118 mg, 57%) as a colorless liquid: 1H NMR (500 MHz,
[D6]acetone): d=7.82 (d, J=15.7 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H),
6.86 (d, J=9.4 Hz, 2H), 6.84 (d, J=15.7 Hz, 1H), 6.82 (d, J=9.4 Hz,
2H), 6.60 (d, J=2.2 Hz, 1H), 6.54 (dd, J=2.2, 8.4 Hz, 1H), 4.12 (t,
J=6.4 Hz, 2H), 3.97 (t, J=6.4 Hz, 2H), 3.82 (s, 3H), 3.71 (s, 3H), 1.93
(m, 2H), 1.84 (m, 2H), 1.69 ppm (m, 2H); 13C NMR (125 MHz,
[D6]DMSO): d=162.4, 159.1, 153.9, 153.3, 135.1, 129.8, 116.8, 115.4,
114.5, 105.7, 99.0, 68.2, 68.1, 54.9, 28.9, 28.7, 22.6 ppm; HRMS-ESI:
m/z [MÀH]À calcd for C22H26NO6: 400.1760, found: 400.1766.
(E)-N-Hydroxy-2-[(naphthalen-4-yl)methoxy]-4-methoxycinna-
mide (13e): Following the procedure as described for 13a, reac-
tion of 12e (2.82 g, 8.44 mmol) in THF (40 mL) with ethyl chlorofor-
mate (2.24 mL, 12.67 mmol) and Et3N (3.38 mL, 12.67 mmol) gave
13e (1.38 g, 47%) as a white solid: mp: 152–1658C; 1H NMR
(500 MHz, [D6]DMSO): d=10.55 (s, 1H), 8.84 (s, 1H), 8.13 (d, J=
8.2 Hz, 1H), 7.98 (m, 2H), 7.94 (d, J=8.2 Hz, 1H), 7.69 (d, J=6.7 Hz,
1H), 7.61 (d, J=16.1 Hz, 1H), 7.55 (m, 2H), 7.45 (d, J=8.5 Hz, 1H),
6.90 (s, 1H), 6.60 (d, J=8.5 Hz, 1H), 6.30 (d, J=16.1 Hz, 1H), 5.65
(s, 2H), 3.80 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO): d=163.9,
162.2, 158.1, 133.8, 133.2, 132.7, 131.6, 129.3, 129.0, 128.7, 127.1,
127.0, 126.5, 125.9, 124.3, 117.0, 106.9, 100.4, 68.7, 55.9 ppm;
HRMS-ESI: m/z [M+H]+ calcd for C21H20NO4: 350.1392, found:
350.1390.
(E)-N-Hydroxy-4-methoxy-2-phenylcinnamide (22a): Following
the procedure described for 8a, reaction of 21a (800 mg,
3.15 mmol) in THF (10 mL) with ethyl chloroformate (512 mg,
4.73 mmol) and Et3N (0.88 mL, 6.30 mmol) gave 22a (355 mg,
42%) as
a
white solid: mp: 100–1028C; 1H NMR (500 MHz,
[D6]acetone): d=8.67 (brs, 1H), 7.66 (d, J=8.2 Hz, 1H), 7.55 (d, J=
15.5 Hz, 1H), 7.47 (m, 2H), 7.39 (m, 1H), 7.33 (d, J=8.4 Hz, 2H),
6.98 (dd, J=2.5, 8.7 Hz, 1H), 6.88 (d, J=2.5 Hz, 1H), 6.41 (d, J=
15.5 Hz, 1H), 3.89 ppm (s, 3H); 13C NMR (125 MHz, [D6]acetone):
d=164.7, 161.3, 145.1, 141.1, 138.6, 130.5, 129.1, 128.8, 128.4,
128.1, 126.4, 117.3, 115.9, 114.9, 114.7, 55.8 ppm; HRMS-ESI: m/z
[M+Na]+ calcd for C16H15NNaO3: 292.0950, found: 292.0944.
(E)-N-Hydroxy-2-(2-(4-methoxyphenoxyoxy)ethoxy)-4-methoxy-
cinnamide (18a): Following the procedure described for 8a, reac-
tion of 17a (900 mg, 2.61 mmol) in THF (10 mL) with ethyl chloro-
formate (424 mg, 3.92 mmol) and Et3N (0.73 mL, 5.22 mmol) gave
18a (497 mg, 53%) as a white solid: mp: 110–1158C; 1H NMR
(500 MHz, [D6]acetone): d=10.12 (s, 1H), 8.63 (s, 1H), 7.85 (d, J=
15.8 Hz, 1H), 7.49 (d, J=8.5 Hz, 1H), 6.95 (d, J=8.1 Hz, 2H), 6.86
(d, J=8.1 Hz, 2H), 6.68 (d, J=2.4 Hz, 1H), 6.57 (dd, J=2.4, 8.5 Hz,
1H), 6.54 (d, J=15.8 Hz, 1H), 4.42 (m, 2H), 4.38 (m, 2H), 3.83 (s,
3H), 3.73 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO): d=162.1,
158.4, 158.3, 154.1, 152.8, 133.7, 129.4, 117.2, 116.9, 116.2, 115.1,
113.2, 107.0, 100.0, 67.7, 67.3, 60.4, 55.9, 55.8 ppm; HRMS-EI: m/z
[M]+ calcd for C19H21NO6: 359.1369, found: 359.1364.
(E)-N-Hydroxy-4-methoxy-2-(4-bromophenyl)cinnamide
(22b):
Following the procedure described for 8a, reaction of 21b
(500 mg, 1.51 mmol) in THF (10 mL) with ethyl chloroformate
(245 mg, 2.27 mmol) and Et3N (0.42 mL, 3.02 mmol) gave 22b
1
(204 mg, 39%) as a white solid: mp: 141–1448C; H NMR (500 MHz,
[D6]DMSO): d=10.64 (s, 1H), 8.90 (s, 1H), 7.65 (d, J=8.2 Hz, 2H),
7.63 (d, J=8.7 Hz, 1H), 7.25 (d, J=8.2 Hz, 2H), 7.22 (d, J=15.6 Hz,
1H), 7.02 (dd, J=2.1, 8.7 Hz, 1H), 6.84 (d, J=2.1 Hz, 1H), 6.28 (d,
J=15.6 Hz, 1H), 3.80 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO):
d=163.4, 160.3, 142.6, 139.4, 136.4, 132.1, 131.8, 128.3, 125.6,
121.7, 118.6, 115.4, 115.1, 55.9 ppm. HRMS-ESI: m/z [M+Na]+ calcd
for C16H14BrNNaO3: 370.0055, found: 370.0049.
(E)-N-Hydroxy-2-(2-(4-methoxyphenoxyoxy)propoxy)-4-methoxy-
cinnamide (18b): Following the procedure described for 8a, reac-
tion of 17b (300 mg, 0.84 mmol) in THF (10 mL) with ethyl chloro-
formate (136 mg, 1.26 mmol) and Et3N (0.23 mL, 1.68 mmol) gave
18b (191 mg, 61%) as a white solid: mp: 115–1208C; 1H NMR
(500 MHz, [D6]acetone): d=10.60 (s, 1H), 8.86 (s, 1H), 7.57 (d, J=
15.9 Hz, 1H), 7.41 (d, J=8.6 Hz, 1H), 6.86 (d, J=9.2 Hz, 2H), 6.82
(d, J=9.2 Hz, 2H), 6.60 (d, J=2.3 Hz, 1H), 6.54 (dd, J=2.3, 8.6 Hz,
1H), 6.38 (d, J=15.9 Hz, 1H), 4.18 (t, J=6.2 Hz, 2H), 4.07 (t, J=
6.2 Hz, 2H), 3.75 (s, 3H), 3.66 (s, 3H), 2.19 ppm (q, J=6.2 Hz, 2H);
13C NMR (125 MHz, [D6]DMSO): d=164.2, 162.1, 158.7, 153.9, 152.9,
134.0, 130.1, 117.3, 116.7, 115.9, 115.1, 106.6, 99.6, 65.5, 65.2, 55.9,
55.8, 29.1 ppm; HRMS-ESI: m/z [M+Na]+ calcd for C20H23NNaO6:
396.1408, found: 396.1418.
(E)-N-Hydroxy-4-methoxy-2-(naphthalen-1-yl)cinnamide
(22c):
Following the procedure described for 8a, reaction of 21c (1.00 g,
3.29 mmol) in THF (15 mL) with ethyl chloroformate (533 mg,
4.93 mmol) and Et3N (0.92 mL, 6.58 mmol) gave 22c (619 mg, 59%)
as a white solid: mp: 125–1278C; 1H NMR (500 MHz, [D6]DMSO):
d=8.00 (d, J=8.2 Hz, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.59 (t, J=
7.9 Hz, 1H), 7.52 (t, J=7.2 Hz, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.33 (d,
J=6.8 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.11 (dd, J=2.6, 8.8 Hz, 1H),
6.83 (d, J=15.6 Hz, 1H), 6.82 (d, J=2.5 Hz, 1H), 6.25 (d, J=15.6 Hz,
1H), 3.79 ppm (s, 3H); 13C NMR (125 MHz, [D6]DMSO): d=163.3,
160.3, 142.4, 137.9, 136.2, 133.6, 132.0, 128.8, 128.6, 127.7, 127.5,
(E)-N-Hydroxy-2-(2-(4-methoxyphenoxyoxy)butoxy)-4-methoxy-
cinnamide (18c): Following the procedure described for 8a, reac-
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