The Journal of Organic Chemistry
Article
140.0, 140.00, 132.4, 130.3, 129.6, 126.4, 126.3, 122.4, 120.0, 117.0,
111.1, 110.0, 108.2, 15.9, 15.3; ESI-MS m/z 243.0 [M + H]+; HRMS
(ESI-TOF) calcd for C13H11N2O3 [M + H]+ 243.0770, found
243.0763.
3-(Pyridin-2-yl)benzo[d]isoxazole-4,7-diol (6c): yellow solid, 75
mg, 33% yield; 1H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 9.74
(s, 1H), 8.84(d, J = 4.4 Hz, 1H), 8.22−8.17 (m, 1H), 7.73 (dd, J = 7.6
Hz, 5.0 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.53 (d, J = 8.2 Hz, 2H);
13C NMR (100 MHz, DMSO-d6) δ 157.0, 154.7, 150.2, 148.7, 147.0,
(100 MHz, DMSO-d6) δ 168.6, 157.8, 154.7, 152.5, 140.7, 130.7,
127.6, 125.8, 123.4, 121.9, 119.3, 110.5, 24.1, 22.1, 21.8, 21.6, 21.0;
ESI-MS m/z 339.2 [M + H]+; HRMS (ESI-TOF) calcd for
C19H19N2O4 [M + H]+ 339.1345, found 339.1338; mp 162−164 °C.
5-tert-Butyl-3-(pyridin-2-yl)benzo[d]isoxazole-4,7-diol and 6-tert-
butyl-3-(pyridin-2-yl) benzo[d]isoxazole-4,7-diol (6l and 6m, 6l:6m
= 1:0.78): yellow solid, 269 mg, 95% yield; 1H NMR (400 MHz,
DMSO-d6), 6l: δ 13.42 (s, 1H), 12.61 (s, 1H), 9.56 (s, 1H), 8.92−8.83
(m, 1H), 8.43 (t, J = 9.2 Hz, 1H), 7.05 (s, 1H), 1.42 (s, 9H); 1H NMR
(400 MHz, DMSO-d6) (6m) δ 13.42 (s, 1H), 12.61 (s, 1H), 9.30 (s,
1H), 8.21 (t, J = 7.0 Hz, 1H), 7.84−7.66 (m, 1H), 6.62 (s, 1H), 1.42
(s, 9H); 13C NMR (100 MHz, DMSO-d6) (6l + 6m) δ 156.6, 156.2,
152.4, 150.1, 148.4, 147.9, 146.8, 143.3, 142.2, 141.0, 140.0, 137.3,
134.0, 131.8, 130.6, 128.9, 126.4, 125.1, 122.5, 122.4, 116.7, 111.1,
107.9, 107.5, 35.00, 34.4, 29.5; ESI-MS m/z 285.4 [M + H]+. HRMS
(ESI-TOF) calcd for C16H17N2O3 [M + H]+ 285.1239, found
285.1229.
144.7, 140.5, 133.7, 126.9, 122.9, 118.4, 109.2; ESI-MS m/z 229.0 [M
+ H]+; HRMS (ESI-TOF) calcd for C12H9N2O3 [M + H]+ 229.0608,
found 229.0602; mp 122−123 °C.
3-(4,7-Dihydroxy-3-(4-isopropylphenyl)benzo[d]isoxazol-5-yl)-
propanoic acid and 3-(4,7-dihydroxy-3-(4-isopropylphenyl)benzo-
[d]isoxazol-6-yl)propanoic acid (6d and 6e, 6d:6e = 1:0.15): yellow
solid, 85 mg, 25% yield; 1H NMR (400 MHz, DMSO-d6) (6d) δ 10.19
(s, 1H), 9.50 (s, 1H), 7.89 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.1 Hz,
2H), 6.72 (s, 1H), 3.04−2.85 (m, 1H), 2.72−2.58 (m, 2H), 2.37−2.19
5-tert-Butyl-3-(3,4,5-trimethoxyphenyl)benzo[d]isoxazole-4,7-
diol and 6-tert-butyl-3-(3,4,5- trimethoxyphenyl)benzo[d]isoxazole-
4,7-diol (6n and 6o, 6n:6o = 1:0.3): yellow solid, 339 mg, 91% yield;
1H NMR (400 MHz, DMSO-d6) (6n) δ 10.05 (s, 1H), 9.22 (s, 1H),
1
(m, 2H), 1.24 (d, J = 6.9 Hz, 6H), H NMR (400 MHz, DMSO-d6)
(6e) δ 10.19 (s, 1H), 9.50 (s, 1H), 7.81 (d, J = 8.1 Hz, 2H), 7.17 (d, J
= 8.1 Hz, 2H), 6.59 (s, 1H), 3.04−2.85 (m, 1H), 2.72−2.58 (m, 2H),
2.37−2.19 (m, 2H), 1.24 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz,
DMSO-d6) (6d) δ 179.3, 173.3, 160.3, 151.8, 130.0, 129.8, 126.9,
126.6, 124.5, 114.9, 68.3, 33.9, 33.8, 33.5, 28.6, 24.1; ESI-MS m/z
342.2 [M + H]+; HRMS (ESI-TOF) calcd for C19H20NO5 [M + H]+
342.1336, found 342.1335.
7.41 (s, 2H), 6.70 (s, 1H), 3.85 (s, 6H), 3.74 (s, 3H), 1.40 (s, 9H); 1H
NMR (400 MHz, DMSO-d6) (6o) δ 10.05 (s, 1H), 9.22 (s, 1H), 7.33
(s, 2H), 6.89 (s, 1H), 3.85 (s, 6H), 3.74 (s, 3H), 1.40 (s, 9H); 13C
NMR (100 MHz, DMSO-d6) (6n) δ 157.3, 156.4, 153.1, 143.4, 139.0,
131.2, 123.7, 108.3, 107.6, 106.9, 103.7, 60.1, 55.9, 34.9, 29.5; ESI-MS
m/z 374.2 [M + H]+; HRMS (ESI-TOF) calcd for C20H24NO6 [M +
H]+ 374.1604, found 374.1627.
3-(4,7-Dihydroxy-3-(pyridin-2-yl)benzo[d]isoxazol-5-yl)propanoic
acid and 3-(4,7-Dihydroxy-3- (pyridin-2-yl)benzo[d]isoxazol-6-yl)-
propanoic acid (6f and 6g, 6f:6g = 1:0.72): yellow solid, 57 mg, 19%
5-tert-Butyl-3-(4-ethoxy-3-methoxyphenyl)benzo[d]isoxazole-
4,7-diol and 6-tert-butyl-3-(4-ethoxy- 3-methoxyphenyl)benzo[d]-
isoxazole-4,7-diol (6p and 6q, 6p:6q =1:0.67): yellow solid, 292 mg,
82% yield; 1H NMR (400 MHz, DMSO-d6) (6p) δ 9.96 (s, 1H), 9.71
(s, 1H), 9.18 (s, 1H), 7.68−7.59 (m, 1H), 7.13−7.06 (m, 1H), 6.99 (s,
1H), 4.10 (q, J = 6.9 Hz, 2H), 3.82 (s, 3H), 1.38 (dd, J = 9.4 Hz, 4.7
Hz, 12H); 1H NMR (400 MHz, DMSO-d6) (6q) δ 9.96 (s, 1H, OH),
9.71 (s, 1H), 8.10 (s, 1H), 7.50−7.43 (m, 1H), 7.13−7.06 (m, 1H),
6.99 (s, 1H), 4.10 (q, J = 6.9 Hz, 2H), 3.82 (s, 3H), 1.38 (dd, J = 9.4
Hz, 4.7 Hz, 12H); 13C NMR (100 MHz, DMSO-d6) (6p + 6q) δ
157.9, 157.2, 156.3, 151.9, 149.4, 149.3, 148.5, 148.4, 143.5, 140.6,
138.9, 134.3, 131.1, 122.4, 122.1, 121.1, 120.8, 115.4, 114.8, 113.2,
113.1, 112.4, 112.3, 108.4, 107.3, 63.8, 63.7, 55.5, 55.4, 34.8, 34.4, 30.3,
29.5, 29.4, 26.3, 14.7; ESI-MS m/z 358.3 [M + H]+; HRMS (ESI-
TOF) calcd for C20H24NO5 [M + H]+ 358.1654, found 358.1646.
5-tert-Butyl-3-(3-chlorophenyl)benzo[d]isoxazole-4,7-diol and 6-
tert-butyl-3-(3- chlorophenyl) benzo[d]isoxazole-4,7-diol (6r and
1
yield; H NMR (600 MHz, DMSO-d6), 6f: δ 13.13 (s, 1H), 12.75 (s,
1H), 8.85 (s, 1H), 7.72 (m, 2H), 7.14 (m, 1H), 6.89 (s, 1H), 2.82 (d, J
1
= 7.4 Hz, 2H), 1.95 (d, J = 24.0 Hz, 2H); H NMR (600 MHz,
DMSO-d6) (6g) δ 13.13 (s, 1H), 12.75 (s, 1H), 8.41 (m, 1H), 8.19
(m, 2H), 6.79 (m, 1H), 6.51 (s, 1H), 2.82 (d, J = 7.4 Hz, 2H), 1.95 (d,
J = 24.0 Hz, 2H); 13C NMR (150 MHz, DMSO-d6) (6f + 6g) δ 173.9,
159.4, 156.4, 153.1, 152.0, 149.7, 149.4, 148.9, 148.3, 148.1, 146.6,
141.2, 140.0, 139.9, 137.3, 136.9, 136.7, 132.5, 127.7, 126.3, 125.2,
123.9, 122.4, 120.3, 119.7, 119.3, 110.3, 110.1, 34.0, 25.2; ESI-MS m/z
301.1 [M + H]+; HRMS (ESI-TOF) calcd for C15H13N2O5 [M + H]+
301.0819, found 301.0806.
3-(Pyridin-2-yl)-5,6,7,8-tetrahydronaphtho[2,3-d]isoxazole-4,9-
diol (6h): yellow solid, 237 mg, 84% yield; 1H NMR (400 MHz,
DMSO-d6) δ 12.99 (s, 1H), 9.03 (s, 1H), 8.86 (d, J = 4.1 Hz, 1H),
8.41 (d, J = 7.9 Hz, 1H), 8.19 (t, J = 7.4 Hz, 1H), 7.81−7.65 (m, 1H),
2.70 (d, J = 27.6 Hz, 4H), 1.72 (s, 4H); 13C NMR (100 MHz, DMSO-
d6) δ 156.3, 152.7, 148.2, 146.8, 141.1, 139.9, 129.6, 129.1, 126.2,
122.3, 117.7, 107.0, 24.0, 23.3, 22.0, 21.9; ESI-MS m/z 283.1 [M +
H]+; HRMS (ESI-TOF) calcd for C16H15N2O3 [M + H]+ 283.1077,
found 283.1073; mp 149−151 °C.
1
6s, 6r:6s = 1:0.08): yellow solid, 250 mg, 79% yield; H NMR (400
MHz, DMSO-d6), 6r: δ 10.04 (s, 1H), 9.27 (s, 1H), 8.08 (s, 1H), 7.95
(d, J = 7.3 Hz, 1H), 7.63−7.45 (m, 2H), 6.68 (s, 1H), 1.38 (s, 9H,);
1H NMR (400 MHz, DMSO-d6) (6s) δ 10.04 (s, 1H), 9.27 (s, 1H),
3-(2-Methoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d]-
8.16, (s, 1H), 8.04 (d, J = 7.3 Hz, 1H), 7.72−7.65 (m, 2H), 6.75 (s,
1H), 1.32 (s, 9H); 13C NMR (100 MHz, DMSO-d6) (6r) δ 156.4,
156.3, 143.4, 139.4, 133.0, 131.2, 130.6, 130.3, 129.8, 129.1, 127.8,
108.1, 107.5, 34.9, 29.5; ESI-MS m/z 318.1 [M + H]+; HRMS (ESI-
TOF) calcd for C17H17ClNO3 [M + H]+ 318.0897, found 318.0890.
5-tert-Butyl-3-(2,4-dichlorophenyl)benzo[d]isoxazole-4,7-diol
and 6-tert-butyl-3-(2,4- dichlorophenyl)benzo[d]isoxazole-4,7-diol
1
isoxazole-4,9-diol (6i): yellow solid, 221 mg, 71% yield; H NMR
(400 MHz, DMSO-d6) δ 7.63−7.52 (m, 1H), 7.42 (dd, J = 7.5 Hz, 1.7
Hz, 1H), 7.22 (d, J = 8.3 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 3.73 (s,
3H), 2.42 (d, J = 25.1 Hz, 4H), 1.66 (d, J = 2.7 Hz, 4H); 13C NMR
(100 MHz, DMSO-d6) δ 180.1, 175.1, 164.1, 157.6, 157.2, 143.5,
143.3, 132.4, 130.4, 120.3, 118.2, 115.1, 111.8, 55.7, 22.7, 22.0, 20.5,
18.6; ESI-MS m/z 312.2 [M + H]+; HRMS (ESI-TOF) calcd for
C18H18NO4 [M + H]+ 312.1236, found 312.1229; mp 129−131 °C.
3-(4-Isopropylphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d]-
1
(6t and 6u, 6t:6u = 1:0.15): yellow solid, 309 mg, 88% yield; H
NMR (400 MHz, DMSO-d6) (6t) δ 9.63 (s, 1H), 9.30 (s, 1H), 7.63−
7.55 (m, 3H), 6.64 (s, 1H), 1.40 (s, 9H); 1H NMR (400 MHz,
DMSO-d6) (6u) δ 9.63 (s, 1H), 9.30 (s, 1H), 7.63−7.55 (m, 3H), 6.64
(s, 1H), 1.34 (s, 9H); 13C NMR (100 MHz, DMSO-d6) (6t) δ 155.5,
154.8, 143.8, 140.2, 139.5, 135.3, 134.4, 132.9, 131.0, 129.1, 127.3,
110.0, 107.3, 35.0, 29.6; ESI-MS m/z 352.2 [M + H]+; HRMS (ESI-
TOF) calcd for C17H16Cl2NO3 [M + H]+ 352.0507, found 352.0517.
N-(4-(5-tert-Butyl-4,7-dihydroxybenzo[d]isoxazol-3-yl)phenyl)-
acetamide and N-(4-(6-tert-butyl-4,7- dihydroxybenzo[d]isoxazol-
3-yl)phenyl)acetamide (6v and 6w, 6v:6w = 1:0.1): yellow solid, 302
mg, 89% yield; 1H NMR (400 MHz, DMSO-d6) (6v) δ 10.15 (s, 1H),
9.91 (s, 1H), 9.19 (s, 1H), 7.95 (d, J = 8.5 Hz, 2H), 7.71 (d, J = 8.4
Hz, 2H), 7.50 (d, J = 8.4 Hz, 0,2H), 6.67 (s, 1H), 2.09 (s, 3H), 1.40 (s,
1
isoxazole-4,9-diol (6j): yellow solid, 261 mg, 81% yield; H NMR
(400 MHz, DMSO-d6) δ 7.92 (d, J = 8.1 Hz, 2H), 7.40 (d, J = 8.0 Hz,
2H), 2.95 (dt, J = 13.5 Hz, 6.7 Hz, 1H), 2.42 (d, J = 25.1 Hz, 4H), 2.39
(s, 4H), 1.62 (s, 2H), 1.22 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz,
DMSO-d6) δ 180.6, 175.0, 165.1, 159.3, 151.8, 144.3, 140.9, 128.9,
126.6, 123.5, 116.8, 109.3, 33.4, 23.6, 22.9, 21.9, 20.5; ESI-MS m/z
324.3 [M + H]+; HRMS (ESI-TOF) calcd for C20H22NO3 [M + H]+
324.1600, found 324.1609; mp 143−144 °C.
N-(4-(4,9-Dihydroxy-5,6,7,8-tetrahydronaphtho[2,3-d]isoxazol-3-
1
yl)phenyl)acetamide (6k): yellow solid, 287 mg, 85% yield; H NMR
(400 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.02 (d, J = 8.7 Hz, 2H), 7.77
(d, J = 8.6 Hz, 2H), 2.51 (s, 4H), 2.10 (s, 3H), 1.68 (s, 4H); 13C NMR
9H); H NMR (400 MHz, DMSO-d6) (6w) δ 10.15 (s, 1H), 9.91 (s,
1
H
dx.doi.org/10.1021/jo401077q | J. Org. Chem. XXXX, XXX, XXX−XXX