The Journal of Organic Chemistry
Article
5.6, 1.2 Hz, 1H), 7.34 (d, J = 1.6 Hz, 1H), 7.17 (t, J = 5.8 Hz, 2H),
6.96 (d, J = 5.6 Hz, 1H), 6.69 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 170.6, 164.7, 163.1, 162.2,
150.9, 149.4, 128.84, 128.79, 125.6, 125.5, 120.4, 119.3, 116.2, 116.0,
111.4, 108.8, 96.3, 56.2, 56.1; HRMS (ESI) m/z: calcd for
C17H15FNO3 [M + H]+, 300.1036; found, 300.1030.
5-(4-(Trifluoromethyl)phenyl)-3-(3,4,5-trimethoxyphenyl)-
isoxazole (3e). White solid (234 mg, 79%), mp 108−109 °C; Rf 0.42
(1:9 EtOAc/hexane); IR (neat, cm−1): 3109, 2845, 1512, 1450, 1054;
1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 8.4 Hz, 2H), 7.75 (d, J =
8.4 Hz, 2H), 7.09 (s, 2H), 6.90 (s, 1H), 3.95 (s, 6H), 3.92 (s, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 168.8, 163.1, 153.7, 139.9,
132.1, 131.8, 130.5, 126.15, 126.10, 126.07, 126.04, 125.1, 124.1,
122.4, 104.2, 98.9, 60.9, 56.3; HRMS (ESI) m/z: calcd for
C19H17F3NO4 [M + H]+, 380.1110; found, 380.1017.
181.8, 157.3, 131.4, 127.5, 127.2, 126.9, 96.6, 32.8, 28.8; HRMS (ESI)
m/z: calcd for C11H14NOS [M + H]+, 208.0796; found, 208.0825.
5-(Furan-2-yl)-3-(thiophen-2-yl)isoxazole (3k). White solid (210
mg, 85%); mp 134−136 °C; Rf 0.52 (1:9 EtOAc/hexane); IR (neat,
1
cm−1): 3255, 3001, 1669, 1596, 1543, 755; H NMR (600 MHz,
CDCl3): δ 7.55 (s, 1H), 7.50 (d, J = 4.2 Hz, 1H), 7.43 (d, J = 5.4 Hz,
1H), 7.13 (d, J = 4.2 Hz, 1H), 6.94 (d, J = 3.6 Hz, 1H), 6.67 (s, 1H),
6.55 (d, J = 4.2 Hz, 1H); 13C{H} NMR (150 MHz, CDCl3): δ 157.9,
144.8, 144.3, 127.9, 127.8, 127.7, 112.1, 111.9, 110.9, 96.7; HRMS
(ESI) m/z: calcd for C11H8NO2S [M + H]+, 218.0276; found,
218.0233.
3-(1-Methyl-1H-pyrrol-2-yl)-5-(4-(trifluoromethyl)phenyl)-
isoxazole (3l). Off-white solid (247 mg, 80%); mp 112−114 °C; Rf
0.48 (1:9 EtOAc/hexane); IR (neat, cm−1): 3255, 3001, 1669, 1596,
1543, 755; 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.0 Hz, 2H),
7.74 (d, J = 8.0 Hz, 2H), 6.79 (t, J = 2.4 Hz, 1H), 6.78 (s, 1H), 6.62
(dd, J = 4.0, 1.6 Hz, 1H), 6.23 (dd, J = 3.8, 2.6 Hz, 1H), 4.00 (s, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 167.0, 157.2, 132.3, 131.9,
5-(2-Methoxyphenyl)-3-(4-methoxyphenyl)isoxazole (3f). Yellow
liquid (270 mg, 77%); Rf 0.35 (1:9 EtOAc/hexane); IR (neat, cm−1):
1
2947, 2509, 1733, 1558, 980; H NMR (600 MHz, CDCl3): δ 8.01
131.7, 131.3, 130.5, 127.8, 126.95, 126.09, 126.05, 126.01, 125.9,
125.1, 122.4, 121.9, 119.7, 112.7, 108.4, 99.9, 37.2; HRMS (ESI) m/z:
calcd for C15H12F3N2O [M + H]+, 293.0902; found, 293.0872.
3-(4-(Methylthio)phenyl)-5-(thiazol-2-yl)isoxazole (3m). Yellow
liquid; (230 mg, 80%); Rf 0.48 (1:9 EtOAc/hexane); IR (neat, cm−1):
(d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.8 Hz, 2H), 7.41 (t, J = 7.5 Hz. 1H),
7.08 (t, J = 7.5 Hz, 1H), 7.04 (s, 1H), 7.02 (d, J = 7.8 Hz, 1H), 6.99
(d, J = 7.8 Hz, 2H), 3.99 (s, 3H), 3.86 (s, 3H); 13C{H} NMR (150
MHz, CDCl3): δ 170.9, 161.8, 161.4, 132.9, 131.4, 130.5, 129.9,
127.6, 125.4, 123.1, 120.1, 114.6, 96.1, 56.4, 55.9; HRMS (ESI) m/z:
calcd for C17H16NO3 [M + H]+, 282.1130; found, 282.1106.
1
3255, 3001, 1669, 1596, 1543, 755; H NMR (400 MHz, CDCl3): δ
8.01 (d, J = 3.2 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 3.2 Hz,
1H), 7.34 (d, J = 8.4 Hz, 2H), 7.16 (s, 1H), 2.54 (s, 3H); 13C{H}
NMR (100 MHz, CDCl3); 164.5, 162.8, 154.4, 144.5, 141.9, 127.2,
126.3, 124.8, 121.4, 99.7, 15.3; HRMS (ESI) m/z: calcd for
C13H11N2OS2 [M + H]+, 275.0313; found, 275.0287.
3-(2-((4-Methoxybenzyl)oxy)phenyl)-5-(pyridin-4-yl)isoxazole
(3g). Yellow solid (230 mg, 84%); mp 130−131 °C; Rf 0.45 (2:8
1
EtOAc/hexane); IR (neat, cm−1): 3109, 2945, 1675, 1558, 1213; H
NMR (400 MHz, CDCl3): δ 8.71 (dd, J = 4.6, 1.8 Hz, 2H), 8.01 (dd,
J = 7.6, 1.6 Hz, 1H), 7.55 (dd, J = 4.6, 1.8 Hz, 2H), 7.43−7.41 (m,
1H), 7.39 (d, J = 8.8 Hz, 2H), 7.37 (s, 1H), 7.18−7.09 (m, 2H),
7.07−6.93 (m, 2H), 5.12 (s, 2H), 3.83 (s, 3H); 13C{H} NMR (100
MHz, CDCl3): δ 166.4, 160.7, 159.7, 156.5, 150.7, 134.5, 131.5,
129.3, 129.2, 128.5, 121.4, 119.4, 117.8, 114.1, 113.2, 103.9, 70.7,
55.3; HRMS (ESI) m/z: calcd for C22H19N2O3 [M + H]+, 359.1396;
found, 359.0688.
2-(5-(Pyridin-4-yl)isoxazol-3-yl)phenol (3g′). Orange solid (250
mg, 95%); mp 127−128 °C; Rf 0.62 (2:8 EtOAc/hexane); IR (neat,
cm−1): 3540, 3109, 2945, 1675, 1558; 1H NMR (400 MHz, CDCl3):
δ 10.33 (br s, 1H), 8.88 (s, 2H), 8.06 (d, J = 5.6 Hz, 2H), 7.76 (s,
1H), 7.78 (dd, J = 7.8, 6.2 Hz, 1H), 7.36 (td, J = 8.6, 1.8 Hz, 1H),
7.06 (d, J = 8.0 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H); 13C{H} NMR (100
MHz, CDCl3): δ 165.6, 161.1, 155.6, 149.1, 135.1, 131.6, 128.6,
120.2, 119.4, 116.6, 114.6, 104.9; HRMS (ESI) m/z: calcd for
C14H11N2O2 [M + H]+, 239.0821; found, 239.0795.
5-(1-Methyl-1H-indol-2-yl)-3-phenylisoxazole (3n). Yellow liquid
(220 mg, 82%); Rf 0.51 (1:9 EtOAc/hexane); IR (neat, cm−1): 3255,
1
3001, 1669, 1596, 1543, 755; H NMR (400 MHz, CDCl3): δ 8.24
(d, J = 7.2 Hz, 1H), 7.86 (dd, J = 8.2, 1.4 Hz, 2H), 7.52 (s, 1H),
7.51−7.44 (m, 3H), 7.39−7.27 (m, 3H), 6.79 (s, 1H), 3.85 (s, 3H);
13C{H} NMR (100 MHz, CDCl3): δ 168.9, 158.8, 137.4, 129.9,
128.9, 127.8, 125.8, 125.7, 122.7, 121.7, 120.9, 109.6, 104.9, 97.6,
33.1; HRMS (ESI) m/z: calcd for C18H15N2O [M + H]+, 275.1184;
found, 275.1187.
5-(1-Methyl-1H-indol-3-yl)-5-(pyridin-3-yl)isoxazole (3o). Yellow
liquid (245 mg, 84%); Rf 0.48 (1:9 EtOAc/hexane); IR (neat, cm−1):
1
3255, 3001, 1669, 1596, 1543, 755; H NMR (400 MHz, CDCl3): δ
9.08 (d, J = 2.0, 1H), 8.68 (d, J = 3.6 Hz, 1H), 8.22 (dd, J = 7.0, 1.4
Hz, 1H), 8.16 (dt, J = 7.6, 1.9 Hz, 1H), 7.55 (s, 1H), 7.46−7.28 (m,
4H), 6.89 (s, 1H), 3.87 (s, 3H); 13C{H} NMR (100 MHz, CDCl3): δ
166.1, 158.9, 150.7, 147.0, 137.5, 132.9, 129.2, 125.6, 124.0, 123.8,
122.9, 121.6, 121.1, 109.6, 104.5, 98.6, 33.2; HRMS (ESI) m/z: calcd
for C17H14N3O [M + H]+, 276.1136; found, 276.1138.
5-(4-Chlorophenyl)-3-(thiophen-2-yl)isoxazole (3h). Orange solid
(215 mg, 78%); mp 103−105 °C; Rf 0.48 (1:9 EtOAc/hexane); IR
1
(neat, cm−1): 3111, 2952, 1557, 1081, 755; H NMR (400 MHz,
CDCl3): δ 7.76 (d, J = 8.4 Hz, 2H), 7.52 (dd, J = 3.6, 1.2 Hz, 1H),
7.46 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 1.2 Hz, 1H), 7.14 (dd, J = 5.2,
3.6 Hz, 1H), 6.74 (s, 1H); 13C{H} NMR (100 MHz, CDCl3): δ
169.3, 158.3, 136.5, 130.6, 129.4, 127.74, 127.70, 127.5, 127.1, 125.7,
97.8; HRMS (ESI) m/z: calcd for C13H9ClNOS [M + H]+, and [M +
H + 2]+, 262.0093 and 264.0093; found, 262.0063.
5-(Pyren-1-yl)-3-(thiophen-2-yl)isoxazole (3i). Yellow solid (235
mg, 90%); mp 124−126 °C; Rf 0.52 (1:9 EtOAc/hexane); IR (neat,
cm−1): 3100, 2885, 1650, 1532, 956; 1H NMR (400 MHz, CDCl3): δ
8.61 (d, J = 9.2 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 8.24−8.15 (m,
4H), 8.13 (s, 1H), 8.08−8.05 (m, 2H), 7.62 (d, J = 2.4 Hz, 1H), 7.49
(d, J = 6.4 Hz, 1H), 7.19 (dd, J = 5.2, 3.6 Hz, 1H), 6.95 (s, 1H);
13C{H} NMR (100 MHz, CDCl3): δ 171.1, 158.1, 132.7, 131.2,
130.9, 130.6, 129.2, 128.9, 128.7, 127.74, 127.69, 127.5, 127.2, 126.65,
126.42, 126.13, 125.9, 124.9, 124.7, 124.4, 124.1, 121.5, 101.9; HRMS
(ESI) m/z: calcd for C23H14NOS [M + H]+, 352.0796; found,
352.0737.
N,N-Dimethyl-4-(5-(pyridin-3-yl)isoxazol-3-yl)aniline (3p). Yel-
low solid (254 mg, 88%); mp 121−123 °C; Rf 0.46 (2:8 EtOAc/
1
hexane); IR (neat, cm−1): 3255, 3001, 1669, 1596, 1543, 755; H
NMR (600 MHz, CDCl3): δ 9.06 (s, 1H), 8.69 (d, J = 3.6 Hz, 1H),
8.19 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 9.0 Hz, 2H), 7.41 (dd, J = 7.8,
4.8 Hz, 1H), 6.76 (d, J = 9.0 Hz, 2H), 6.65 (s, 1H), 3.05 (s, 6H);
13C{H} NMR (150 MHz, CDCl3): δ 171.9, 160.4, 151.7, 150.9,
148.1, 134.1, 127.3, 125.9, 123.8, 114.9, 111.9, 94.3, 40.3; HRMS
(ESI) m/z: calcd for C16H16N3O [M + H]+, 266.1293; found,
266.1276.
3,5-Di(pyridin-3-yl)isoxazole (3q). Yellow liquid (260 mg, 79%);
Rf 0.48 (1:9 EtOAc/hexane); IR (neat, cm−1): 3255, 3001, 1669,
1596, 1543, 755; 1H NMR (400 MHz, CDCl3): δ 9.09 (d, J = 3.6 Hz,
2H), 8.72 (d, J = 4.8 Hz, 2H), 8.22 (dt, J = 8.0, 2.0 Hz, 1H), 8.16 (dt,
J = 8.0, 2.0 Hz, 1H), 7.49−7.44 (m, 2H), 6.98 (s, 1H); 13C{H} NMR
(100 MHz, CDCl3): δ 168.3, 160.7, 151.3, 147.9, 147.1, 144.9, 134.1,
133.0, 123.9, 123.5, 98.2; HRMS (ESI) m/z: calcd for C13H10N3O [M
+ H]+, 224.0824; found, 224.0825.
5-(tert-Butyl)-3-(thiophen-2-yl)isoxazole (3j). Yellow liquid (245
mg, 92%); Rf 0.48 (1:9 EtOAc/hexane); IR (neat, cm−1): 3255, 3001,
5-Methyl-3-phenylisoxazole (3r).4b Yellow oil (215 mg, 86%); Rf
1
1
1669, 1596, 1543, 755; H NMR (400 MHz, CDCl3): δ 7.43 (d, J =
0.36 (1:9 EtOAc/hexane); H NMR (400 MHz, CDCl3): δ 7.72−
3.6 Hz, 1H), 7.39 (d, J = 5.2 Hz, 1H), 7.09 (dd, J = 4.8, 3.6 Hz, 1H),
7.69 (m, 2H), 7.37−7.35 (m, 3H), 6.21 (s, 1H), 2.47 (s, 3H); 13C{H}
NMR (100 MHz, CDCl3): δ 168.9, 161.5, 128.8, 128.3, 127.8, 125.7,
6.17 (s, 1H), 1.35 (s, 9H); 13C{H} NMR (100 MHz, CDCl3): δ
K
J. Org. Chem. XXXX, XXX, XXX−XXX