Med Chem Res
CDCl ): d 3.53 (d, J = 13.6 Hz, 2H), 3.81 (s, 3H), 4.91 (s,
1,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
[a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(4-bromo-
2-fluorophenyl)-isoxazole (7g) Yield 63 %; purity by
HPLC: 99.0 %; off-white solid; m.p. 217–219 °C; IR
3
2
H), 6.46 (s, 1H), 7.07 (d, J = 8.8 Hz, 2H), 7.20–7.28 (m,
7
H), 7.46 (d, J = 6.8 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H);
1
3
C NMR (100 MHz, CDCl ): d 27.4, 55.7, 62.6, 77.3,
3
-
1
1
1
1
02.2, 114.9, 121.2, 122.6, 126.8, 127.8, 128.3, 128.6,
(KBr) vmax/cm : 3011, 1611, 1437, 1168, 750; H NMR
31.8, 142.8, 161.2, 161.9, 169.5; MS (ESI) m/z: 446.1
?
(400 MHz, CDCl ): d 3.22 (d, J = 13.2 Hz, 2H), 4.93 (s,
3
[
M ? H] .
2H), 6.36 (s, 1H), 6.81 (d, J = 4.0 Hz, 1H), 7.19–7.28 (m,
6
H), 7.38–7.43 (m, 2H), 7.53 (d, J = 7.2 Hz, 2H), 7.87 (t,
1
1
,1-Difluoro-1,1 a, 6, 10b-tetrahydro- (1 a, 6, 10b)-dibenzo
3
J = 8.8 Hz, 1H); C NMR (100 MHz, CDCl ): d 27.3,
6
3
[
a,e] cyclopropa[c] cyclohepten-6-yloxymethyl-3-(benzo–
1,3]dioxol-5yl)-isoxazole (7c) Yield 50 %; purity by
2.8, 79.4, 103.4, 103.5, 119.9, 120.2, 122.4, 126.1, 127.3,
[
1
28.1, 130.0, 131.5, 141.9, 157.1, 158.6, 161.1, 169.5; MS
HPLC: 99.2 %; off-white solid; m.p. 219–221 °C; IR
?
ESI) m/z: 514 [M ? 2H] .
(
-
1
KBr) vmax/cm : 3008, 1616, 1474, 1168, 749; H NMR
1
(
(
400 MHz, CDCl ): d 3.22 (d, J = 13.2 Hz, 2H), 4.90 (s,
H), 6.04 (s, 2H), 6.35 (s, 1H), 6.61(s, 1H), 6.88 (d,
1,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
[a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(3,4,3-tri-
methoxyphenyl)-isoxazole (7h) Yield 72 %; purity by
HPLC: 97.6 %; white solid; m.p. 190–193 °C; IR (KBr)
3
2
J = 8.0 Hz, 1H), 7.19–7.35 (m, 8H), 7.53 (d, J = 6.8 Hz,
?
H); MS (ESI) m/z: 460.1 [M ? H] .
2
-
1
1
vmax/cm : 3009, 1585, 1463, 1131, 750; H NMR
1
,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
(
400 MHz, CDCl ): d 3.52 (d, J = 13.2 Hz, 2H), 3.72 (s,
3
[a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(4-fluo-
rophenyl)-isoxazole (7d) Yield 65 %; purity by HPLC:
3H), 3.87 (s, 6H), 4.92 (s, 2H), 6.46 (s, 1H), 7.19 (s, 2H),
7.24–7.28 (m, 6H), 7.32 (s, 1H), 7.46 (d, J = 7.2 Hz, 2H);
13
99.8 %; white solid; m.p. 202–205 °C; IR (KBr) vmax/
cm : 3007, 1610, 1459, 1166, 748; H NMR (400 MHz,
C NMR (100 MHz, CDCl ): d 27.3, 56.5, 60.5, 62.6,
-1 1
3
77.3, 102.7, 104.6, 122.6, 124.3, 126.8, 127.8,
CDCl ): d 3.22 (d, J = 13.2 Hz, 2H), 4.92 (s, 2H), 6.35 (s,
3
1
2
6
1
H), 6.67 (s, 1H), 7.14–7.26 (m, 8H), 7.53 (d, J = 7.6 Hz,
1
1,1-Difluoro-1,1a,6,10b-tetrahydro-(1a,6,10b)-dibenzo[a,e]
cyclopropa[c]cyclohepten-6-yloxymethyl-3-thiophene- isoxa-
zole (7i) Yield 65 %; purity by HPLC: 97.0 %; white
3
H), 7.81 (m, 2H); C NMR (100 MHz, CDCl ): d 27.3,
3
2.9, 77.3, 100.8, 115.9, 116.1, 122.4, 126.1, 127.5, 128.1,
-
1
28.7, 131.6, 141.9, 161.5, 162.6, 165.1, 169.7; MS (ESI)
?
solid; m.p. 189–192 °C; IR (KBr) vmax/cm : 3082, 1610,
1
m/z: 434.1 [M ? H] .
1462, 1168, 751; H NMR (400 MHz, CDCl ): d 3.23 (d,
3
J = 13.2 Hz, 2H), 4.91 (s, 2H), 6.35 (s, 1H), 6.63 (s, 1H),
1
,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(4-chlor-
ophenyl)-isoxazole (7e) Yield 60 %; purity by HPLC:
7
1
.12 (m, 1H), 7.19–7.28 (m, 6H), 7.43 (m, 1H), 7.49 (m,
[
1
H), 7.53 (d, J = 8.0 Hz, 2H); C NMR (100 MHz,
3
CDCl ): d 29.6, 62.9, 77.1, 101.0, 122.4, 126.1, 127.5,
3
97.7 %; white solid; m.p. 235–238 °C; IR (KBr) vmax/
cm : 3007, 1610, 1459, 1166, 748; H NMR (400 MHz,
1
27.6, 127.7, 128.1, 130.5, 131.6, 141.9, 157.7, 169.5; MS
-1 1
?
ESI) m/z: 422.1 [M ? H] .
(
CDCl ): d 3.22 (d, J = 13.2 Hz, 2H), 4.92 (s, 2H), 6.35 (s,
3
1
H), 6.67 (s, 1H), 7.19–7.28 (m, 6H), 7.44–7.46 (s, 2H),
1,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
[a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(1-methyl-
1H-pyrazole)-isoxazole (7j) Yield 60 %; purity by HPLC:
97.2 %; off-white solid; m.p. 246–248 °C; IR (KBr) vmax/
1
3
.53 (d, J = 6.8 Hz, 2H), 7.76–7.78 (m, 2H); C NMR
7
(
100 MHz, CDCl ): d 27.33, 63.0, 76.7, 100.9, 122.4,
3
1
26.1, 127.3, 127.8, 128.1, 128.2, 129.2, 131.7, 136.2,
?
41.9, 161.5, 169.9; MS (ESI) m/z: 450 [M ? H] .
-1
1
1
cm : 3008, 1615, 1458, 1167, 749; H NMR (400 MHz,
CDCl ): d 3.22 (d, J = 13.6 Hz, 2H), 3.97 (s, 3H), 4.89 (s,
3
1
,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
2
H), 6.34 (s, 1H), 6.50 (s, 1H), 7.19–7.28 (m, 6H), 7.52 (d,
[
a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-(4-nitro-
1
J = 7.2 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H); C NMR
3
phenyl)-isoxazole (7f) Yield 55 %; purity by HPLC:
9
(
100 MHz, CDCl ): d 27.3, 39.2, 62.3, 77.3, 101.1, 121.3,
3
8.1 %; off-white solid; m.p. 210–213 °C; IR (KBr) vmax/
-1 1
cm : 3009, 1600, 1524, 1165, 751; H NMR (400 MHz,
1
1
26.1, 127.5, 128.1, 128.8, 131.6, 138.6, 141.9, 154.9,
?
69.1; MS (ESI) m/z: 420.1 [M ? H] .
CDCl ): d 3.53 (d, J = 13.2 Hz, 2H), 4.97 (s, 2H), 6.48 (s,
3
1
H), 7.23–7.30 (m, 6H), 7.45 (m, 3H), 8.20 (m, 2H), 8.37
1
1,1-Difluoro-1, 1a,6, 10b-tetrahydro-(1a,6, 10b)-dibenzo
[a,e]cyclopropa[c] cyclohepten-6-yloxymethyl-3-pyridyl-
isoxazole (7k) Yield 62 %; purity by HPLC: 99.3 %; off-
3
(
m, 2H); C NMR (100 MHz, CDCl ): d 27.2, 62.9, 77.3,
3
1
1
01.1, 122.3, 124.2, 126.1, 127.6, 127.7, 128.2, 131.7,
-
1
34.8, 141.7, 148.7, 160.7, 170.7; MS (ESI) m/z: 461
?
white solid; m.p. 221–223 °C; IR (KBr) vmax/cm : 3014,
1
[
M ? H] .
1685, 1458, 1167, 750; H NMR (400 MHz, CDCl ): d
3
1
23