The Journal of Organic Chemistry
Page 16 of 19
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(M)-(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)benzoate
(M)-20: (M)-1-Carboxyphenyl(2-trifluoromethy)benzimidazole (M)-2 (40 mg, 0.13 mmol, 1 eq) and (1R,2S,5R)-
(−)-Menthol (20 mg, 0.13 mmol, 1 eq) purified via column chromatography (hexane:ethylacetate 30:1, column
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dimensions: 1x10 cm). 48 mg of a white foamy solid (85 %). H NMR (500 MHz, CDCl3) δ 8.24 (dd, J = 7.5,
1.9 Hz, 1H), 7.89 (dd, J = 7.9, 1.2 Hz, 1H), 7.69 (ddd, J = 7.6, 7.5, 1.7 Hz, 1H), 7.65 (ddd, J = 7.6, 7.5, 1.4 Hz,
1H), 7.38 (d, J = 7.6 Hz, 1H), 7.33 (ddd, J = 7.9, 7.3, 1.2 Hz, 1H), 7.38 (ddd, J = 8.2, 7.3, 1.3 Hz, 1H), 6.93 (dt, J
= 8.2, 1.0 Hz, 1H), 4.55 (ddd, J = 11.0, 11.0, 4.4 Hz, 1H), 1.66 (m, 1H), 1.45 (m, 1H), 1.34 (m, 1H), 1.23
(m,1H), 0.82 (m,1H), 0.75 (m,1H), 0.75 (d, J = 6.5 Hz, 3H), 0.70 (m,1H), 0.58 (m, 1H), 0.40 (d, J = 7.0 Hz, 3H),
0.36 (d, J = 7.0 Hz, 3H), 0.32 (m, 1H), 13C{1H} NMR (126 MHz, CDCl3) δ 164.0, 141.0 (q, J = 38.3 Hz), 140.7,
138.0, 133.7, 133.4, 133.0, 130.7, 130.2, 130.1, 125.9, 124.0, 121.5, 119.0 (q, J = 272.0 Hz), 111.1, 75.8, 46.3,
40.1, 34.0, 31.4, 25.5, 22.7, 21.9, 20.8, 15.5. 19F NMR (376 MHz, CDCl3) δ -61.38 HRMS (ESI-TOF) m/z:
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[M+H]+ calculated for C25H28O2N2F3: 445.2097.1057 found: 445.2101,
= −3.29° (c= 0.15 MeOH).
(P)-(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-1-
yl)benzoate (P)-21 Using general procedure, from 15 mg of (P)-2 and (-)-Borneol, 17 mg of oil (77 %). Purified
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by column chromatography (hexane:ethylacetate 8.5:1, column dimesions 1x10 cm). H NMR (400 MHz,
CDCl3) δ 8.22 – 8.19 (m, 1H), 7.97 – 7.92 (m, 1H), 7.72 (dqd, J = 14.8, 7.5, 1.7 Hz, 2H), 7.42 (dd, J = 9.5, 1.4
Hz, 1H), 7.42 – 7.33 (m, 2H), 7.04 – 7.01 (m, 1H), 4.84 (ddd, J = 10.0, 3.6, 2.2 Hz, 1H), 2.07 – 1.97 (m, 1H),
1.53 (tdd, J = 12.0, 8.0, 4.4 Hz, 1H), 1.46 (t, J = 4.5 Hz, 1H), 1.17 (ddd, J = 13.8, 9.5, 4.6 Hz, 1H), 1.09 – 1.00
(m, 1H), 0.76 (s, J = 4.4 Hz, 3H), 0.75 (s, 3H), 0.74 – 0.67 (m, 1H), 0.64 (s, 3H), 0.24 (dd, J = 13.9, 3.6 Hz, 1H).
13C NMR{1H} (101 MHz, CDCl3) δ 165.3, 140.8 (q, J = 38.6 Hz), 140.8, 137.7, 133.4, 133.3, 132.5, 130.6,
130.1, 130.0, 126.1, 124.1, 121.7, 119.0 (q, J = 272.0 Hz), 110.9, 82.2, 48.7, 47.9, 44.6, 35.8, 27.8, 26.9, 19.7,
18.8, 13.4, 19F NMR (376 MHz, CDCl3) δ= -61.65, HRMS (ESI-TOF) m/z: [M+H]+ calculated for
C25H26F3N2O2: 443.1946 found: 443.1941,
= -142.5°(c= 0.08 CHCl3).
(M)-(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl
2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-1-
yl)benzoate (M)-21 Using general procedure, from 15 mg of (M)-2 and (-)-Borneol, 15 mg of oil (68 %).
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Purified by column chromatography (hexane:ethylacetate 8.5:1, column dimesions 1x10 cm). H NMR (400
MHz, CDCl3) δ 8.24 (dd, J = 7.5, 2.0 Hz, 1H), 7.96 – 7.92 (m, 1H), 7.73 (pd, J = 7.5, 1.6 Hz, 2H), 7.44 – 7.33
(m, 3H), 7.08 – 7.02 (m, 1H), 4.95 – 4.90 (m, 1H), 2.14 (ddt, J = 14.0, 10.0, 4.0 Hz, 1H), 1.56 – 1.47 (m, 2H),
1.06 – 0.84 (m, 2H), 0.78 (s, J = 17.4 Hz, 3H), 0.73 (s, 3H) overalps with 0.75– 0.70 (m, 1H), 0.57 (dd, J = 13.8,
3.6 Hz, 1H), 0.50 (s, 3H). 13C NMR {1H} (101 MHz, CDCl3) δ 165.0, 140.9 (q, J = 38.3 Hz), 140.8, 137.7,
133.5, 133.4, 132.6, 130.6, 130.1, 126.1, 124.1, 121.7, 119.0 (q, J = 271.9 Hz), 111.1, 81.8, 48.9, 48.00, 44.7,
36.1, 27.9, 26.8, 19.7, 18.8, 13.2, 19F NMR (376 MHz, CDCl3) δ (ppm) = -61.90, HRMS (ESI-TOF) m/z:
[M+H]+ calculated for C25H26F3N2O2: 443.1946 found: 443.1942,
= -3.33°(c= 0.09 CHCl3).
(P)-(3S,8S,9S,10R,13R,14S,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,
15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-
1-yl)benzoate (P)-22 : (P)-1-Carboxyphenyl(2-trifluoromethy)benzimidazole (P)-2 (40 mg, 0.13 mmol, 1 eq)
and cholesterol (50 mg, 0.13 mmol, 1 eq) purified via column chromatography (hexane:ethylacetate 9:1, column
dimensions: 1x10 cm). 64 mg of white foamy solid (72 %). 1H NMR (500MHz, CDCl3): δ 8.20 (dd, J = 7.6, 1.6
Hz, 1H), 7.88 (dd, J = 7.8, 1.3 Hz, 1H), 7.69 (ddd, J = 7.6, 7.5, 1.8 Hz, 1H), 7.64 (ddd, J = 7.6, 7.5, 1.5 Hz, 1H),
7.44 (d, J = 7.5 Hz, 1H), 7.33 (ddd, J = 7.8, 7.5, 1.1 Hz, 1H), 7.28 (td, J = 7.8, 7.5, 1.1 Hz, 1H), 6.91 (dd, J = 7.8,
1.3 Hz, 1H), 5.04 (m, 1H), 4.34 (dddd, J = 10.8, 10.8, 4.5 Hz, 1H), 0.50 (d, J = 7.0 Hz, 3H), 0.50 (d, J = 7.0 Hz,
3H), 0.50 (d, J = 7.0 Hz, 3H), 0.69 (s, 3H), 0.59 (s, 3H), 0.70 - 1.92 (overlapping multiplets) 13C{1H} NMR,
126MHz, CDCl3: δ 163.9, 141.2 (q, J =38.5), 140.6, 139.3, 138.1, 133.6, 133.6, 132.9, 130.7, 130.1, 130.0,
126.0, 124.0, 122.6, 121.4, 119.0 (q, J = 272.2), 111.0, 75.3, 56.7, 56.2, 50.0, 42.4, 39.8, 39.6, 36.7, 36.6, 36.5,
36.3, 35.9, 31.9, 31.8, 28.3, 29.1, 26.9, 24.4, 23.9, 23.0, 22.7, 21.0, 19.2, 18.8, 11.9 19F NMR (376 MHz, CDCl3)
δ -61.98 HRMS (ESI-TOF) m/z: [M+H]+ calculated for C42H54O2N2F3: 675.4132, found: 675.4137
= -
96.41° (c= 0.64 CHCl3).
(M)-(3S,8S,9S,10R,13R,14S,17R)-10,13-Dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,
15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-(2-(trifluoromethyl)-1H-benzo[d]imidazol-
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