K. Chun et al. / Bioorg. Med. Chem. 16 (2008) 530–535
533
5.1.4. 2-Formyl-4-methoxyphenylmethylglutarate (4e).
1H NMR ðCDCl3; 300 MHzÞ d 9.98 (s, 1H), 7.27 (d,
J ¼ 2:1 Hz, 1H), 7.11–7.01 (m, 2H), 3.77 (s, 3H), 3.63
(s, 3H), 2.67 (t, J ¼ 7:2 Hz, 2H), 2.42 (t, J ¼ 7:1 Hz,
2H), 2.05–1.97 (m, 2H); 13C NMR ðCDCl3Þ d 188.2,
173.0, 171.5, 157.4, 145.3, 128.3, 124.3, 121.7, 113.1,
55.6, 51.5, 32.8, 32.7, 19.7; ESI (m/z) 281.3 ðMNaþÞ.
2H), 2.70 (t, J ¼ 7:4 Hz, 2H), 1.32 (s, 9H); 13C NMR
ðCDCl3Þ d 173.3, 162.0, 151.5, 147.7, 140.8, 128.8,
127.5, 123.9, 119.0, 116.2, 51.9, 34.7, 32.3, 31.6, 26.8;
ESI (m/z) 289.2 ðMNaþÞ.
5.3. General procedures for 2a–f
Methyl-3-(2-oxo-2H-chromen-3-yl)propionate (5, 1 equiv)
was dissolved in MeOH and NH2OK in MeOH was
added at 0 °C. The mixture was stirred for 1–2 h at
room temperature. Then the mixture was filtered
through on a pad of Celite with eluting MeOH and
concentrated in vacuo. Compound was obtained by
flash chromatography (10% methanol in chloroform)
in 18–32% yields.
5.1.5. 4-tert-Butyl-2-formylphenylmethylglutarate (4f).
1H NMR ðCDCl3; 300 MHzÞ d 10.05 (s, 1H), 7.84 (d,
J ¼ 3:3 Hz, 1H), 7.63 (dd, J ¼ 2:6, 2.7 Hz, 1H), 7.08 (d,
J ¼ 8:4 Hz, 1H), 3.68 (s, 3H), 2.72 (t, J ¼ 7:3 Hz, 2H),
2.48 (t, J ¼ 7:0 Hz, 2H), 2.09 (t, J ¼ 7:4 Hz, 2H), 1.33–
1.29 (m, 9H); 13C NMR ðCDCl3Þ d 189.1, 173.3, 171.4,
149.5, 149.1, 132.5, 128.0, 127.3, 122.9, 51.6, 34.6, 33.0,
32.9, 32.8, 31.1, 31.1, 19.8; ESI (m/z) 306.7 ðMNaþÞ.
5.3.1. N-Hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide
(2a). 1H NMR ðCDCl3; 300 MHzÞ d 7.76 (s, 1H),
7.59–7.51 (m, 2H), 7.31–7.28 (m, 2H), 2.85 (t,
J ¼ 7:2 Hz, 2H), 2.45 (t, J ¼ 7:3 Hz, 2H); 13C NMR
ðCDCl3Þ d 170.2, 162.7, 153.6, 141.4, 131.5, 128.1,
127.6, 125.0, 119.8, 116.6, 27.4, 23.8; ESI (m/z) 232.6
ðMNaþÞ.
5.2. General procedures for 5a–f
2-Formylphenylmethylglutarate (4, 1 equiv) was dis-
solved
in
toluene
and
DBU
(1,8-iazabicy-
clo[5.4.0]undec-7-ene) (2 equiv) was added at room
temperature. The mixture was heated by reflux
(150 °C) for 1 day. Then the solvent was removed by ro-
tary evaporator. Compound was obtained by flash chro-
matography (chloroform) in 35–45% yield.
5.3.2. N-Hydroxy-3-(6-methyl-2-oxo-2H-chromen-3-yl)pro-
1
panamide (2b). H NMR ðCDCl3; 300 MHzÞ d 7.61 (s,
1H), 7.25 (d, J ¼ 6:3 Hz, 2H), 7.16 (d, J ¼ 8:1 Hz,
1H), 2.82 (t, J ¼ 7:0 Hz, 2H), 2.43–2.36 (m, 5H); 13C
NMR ðCDCl3Þ d 170.4, 163.0, 151.8, 141.5, 134.9,
132.6, 127.9, 127.5, 119.7, 116.4, 31.4, 27.5, 20.8; ESI
(m/z) 248.2 ðMNaþÞ.
5.2.1. Methyl-3-(2-oxo-2H-chromen-3-yl)propionate (5a).
1H NMR ðCDCl3; 300 MHzÞ d 7.53 (s, 1H), 7.42–7.37
(m, 2H), 7.25–7.16 (m, 2H), 3.60 (s, 3H), 2.82 (t, J ¼
6:9 Hz, 2H), 2.65 (t, J ¼ 7:1 Hz, 2H); 13C NMR
ðCDCl3Þ d 173.2, 171.1, 151.2, 135.2, 2.2, 131.4, 127.9,
126.3, 126.0, 123.7, 123.3, 51.5, 32.8, 19.7; ESI (m/z)
230.5 ðMNaþÞ.
5.3.3. 3-(6-Chloro-2-oxo-2H-chromen-3-yl)-N-hydroxy-pro-
panamide (2c). 1H NMR ðCDCl3; 300 MHzÞ d 7.64–7.24
(m, 4H), 2.85 (t, J ¼ 7:1 Hz, 2H), 2.42 (t, J ¼ 7:3 Hz,
2H); ESI (m/z) 290 ðMNaþÞ.
5.2.2. Methyl 3-(6-methyl-2-oxo-2H-chromen-3-yl)propi-
onate (5b). 1H NMR ðCDCl3; 300 MHzÞ d 7.51 (s, 1H),
7.27–7.16 (m, 3H), 3.64 (s, 3H), 2.86 (t, J ¼ 7:3 Hz, 2H),
2.69 (t, J ¼ 7:1 Hz, 2H), 2.37 (s, 3H); 13C NMR
ðCDCl3Þ d 172.9, 161.6, 151.3, 139.9, 133.9, 131.8,
127.4, 127. 2, 116.0, 51.6, 32.0, 26.5, 20.7; ESI (m/z)
264.2 ðMNaþÞ.
5.3.4. 3-(6-Bromo-2-oxo-2H-chromen-3-yl)-N-hydroxy-pro-
1
panamide (2d). H NMR ðCD3OD; 300 MHzÞ d 7.66–
7.55 (m, 3H), 7.21–7.16 (d, J ¼ 8:7 Hz, 1H), 2.85 (t,
J ¼ 6:3 Hz, 2H), 2.43 (t, J ¼ 6:8 Hz, 2H); ESI (m/z)
335 ðMNaþÞ.
5.2.3. Methyl 3-(6-bromo-2-oxo-2H-chromen-3-yl)propi-
onate (5d). 1H NMR ðCDCl3; 300 MHzÞ d 7.52 (t,
J ¼ 9:4 Hz, 3H), 7.16 (d, J ¼ 8:5 Hz, 1H), 3.64 (s,
3H), 2.86 (t, J ¼ 7:1 Hz, 2H), 2.68 (d, J ¼ 7:1 Hz, 2H);
13C NMR ðCDCl3Þ d 172.8, 161.0, 151.0, 138.6, 133.6,
129.7, 129.1, 120.9, 118.2, 166.9, 50.6, 31.8, 26.6.
5.3.5. N-Hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl)
propanamide (2e). 1H NMR ðCDCl3; 300 MHzÞ d 7.63 (s,
1H), 7.19 (d, J ¼ 8:7 Hz, 1H), 7.04 (dd, J ¼ 2:6, 2.7 Hz,
2H), 6.94 (t, J ¼ 7:3 Hz, 1H), 3.80 (s, 3H), 2.83 (t,
J ¼ 7:0 Hz, 2H), 2.39 (q, J ¼ 7:2 Hz, 2H); 13C NMR
ðCDCl3Þ d 169.4, 162.3, 156.1, 147.5, 140.9, 127.3, 119.7,
118.9, 117.2, 109.6, 30.9, 27.2; ESI (m/z) 264.2 ðMNaþÞ.
5.2.4. Methyl 3-(6-methoxy-2-oxo-2H-chromen-3-yl)pro-
pionate (5e). 1H NMR ðCDCl3; 300 MHzÞ d 7.53 (s,
1H), 7.20 (s, 1H), 7.03 (dd, J ¼ 2:7, 3.0 Hz, 1H), 6.86
(d, J ¼ 3:0 Hz, 1H), 3.81 (s, 3H), 3.81 (s, 3H), 2.86 (t,
J ¼ 7:1 Hz, 2H), 2.69 (t, J ¼ 7:1 Hz, 2H); 13C NMR
ðCDCl3Þ d 172.9, 161.5, 155.9, 147.6, 139.7, 127.9,
119.5, 118.5, 117.3, 109.4, 55.7, 51.5, 31.9, 26.5; ESI
(m/z) 263.2 ðMNaþÞ.
5.3.6. 3-(6-tert-Butyl-2-oxo-2H-chromen-3-yl)-N-hydroxy-
1
propanamide (2f). H NMR ðCDCl3; 300 MHzÞ d 7.76
(s, 1H), 7.63–7.57 (m, 2H), 7.24 (d, J ¼ 8:4 Hz, 1H),
2.84 (t, J ¼ 7:3 Hz, 2H), 2.44 (t, J ¼ 7:3 Hz, 2H), 1.35
(s, 9H); 13C NMR ðCDCl3Þ d 171.5, 163.6, 152.6,
149.0, 142.4, 129.9, 128.2, 125.3, 120.3, 116.7, 35.4,
32.0, 31.7, 28.1; ESI (m/z) 290.2 ðMNaþÞ.
5.2.5. Methyl-3-(6-tert-butyl-2-oxo-2H-chromen-3-yl)propi-
5.4. Procedures for compounds 9a–d
1
onate (5f). H NMR ðCDCl3; 300 MHzÞ 7.58 (s, 1H),
7.50 (dd, J ¼ 2:1, 2.4 Hz, 1H), 7.39 (d, J ¼ 2:4 Hz,
1H), 7.21 (s, 1H), 3.65 (s, 3H), 2.87 (t, J ¼ 7:1 Hz,
5.4.1. 2-(Benzyloxy)-5-methoxybenzaldehyde (6). 2-Hy-
droxy-5-methoxybenzaldehyde (500 mg, 3.29 mmol,