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1825
purified tertiary alcohol was dissolved in abs ethanol
(15 mL). Concd HCl (1.5 mL) was added and the reac-
tion refluxed for 1 h. After evaporating the solvent the
residue was dissolved in CH2Cl2, water was added, the
mixture adjusted to pH 8 with satd NaHCO3 and ex-
tracted with CH2Cl2. The CH2Cl2 layer was washed with
1 N NaOH, water, brine, dried, concentrated and puri-
fied by silica gel flash chromatography using a gradient
of CHCl3–hexanes (1/1) to CHCl3 to 2% CH3OH in
2.78 (t, 2H, NCH2); 2.53 (m, 4H, CH2NCH2); 2.18 (q,
2H, CH2); 1.61 (m, 4H, CH2CH2NCH2CH2); 1.46 (m,
2H, NCH2CH2CH2); 0.76 (t, 3H, CH3).
5.1.12. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(6-hydroxynaphthalen-2-yl)propene,
6a. To 5a (208 mg, 0.41 mmol) dissolved in
DMF (10 mL) was added NaSEt (80%, 0.86 g,
10.2 mmol) and refluxed for 1.5 h. Water was added,
the mixture adjusted to pH 9 with satd NaHCO3, ex-
tracted with EtOAc, washed with water, brine, dried
and concentrated. The residue was purified by silica
gel flash chromatography using a gradient of CHCl3–
hexanes (1/1) to CHCl3 to 3–8% CH3OH in CHCl3 to
1
CHCl3 to give 0.21 g (72%) of 5a. 200 MHz H NMR
(CDCl3) d 6.62–7.80 (m, 14H, ArH); 4.00–4.17 (t, 2H,
OCH2); 3.73–3.95 (s, 6H, OCH3); 2.70–2.86 (t, 2H,
NCH2); 2.54 (m, 4H, CH2NCH2); 2.19–2.22 (s, 3H,
CH3); 1.64 (m, 4H, CH2CH2NCH2CH2); 1.49 (m, 2H,
NCH2CH2CH2).
1
give 0.144 g (73%) of 6a. 400 MHz H NMR (DMSO-
d6) d 9.11–9.63 (s, 2H, OH); 6.37–7.66 (m, 14H, ArH);
3.83–3.93 (t, 2H, OCH2); 2.40–2.60 (t, 2H, NCH2);
2.32 (m, 4H, CH2NCH2); 1.96–1.99 (s, 3H, CH3);
1.40 (m, 4H, CH2CH2NCH2CH2); 1.28 (m, 2H,
NCH2CH2CH2).
5.1.7. (E/Z)-1-(4-Methoxyphenyl)-2-(4-(2-piperidin-1-yl)-
ethoxy)phenyl-1-(6-methoxynaphthalen-1-yl)propene, 5b.
Prepared following the method for 5a using 4b and 1-
iodo-6-methoxynaphthalene.12 Yield 0.185 g (67%).
200 MHz 1H NMR (CDCl3) d 6.47–8.00 (m, 14H,
ArH); 4.09 (t, 2H, OCH2); 3.67–3.93 (s, 6H, OCH3);
2.77 (t, 2H, NCH2); 2.53 (m, 4H, CH2NCH2); 1.84 (s,
3H, CH3); 1.63 (m, 4H, CH2CH2NCH2CH2); 1.48 (m,
2H, NCH2CH2CH2).
5.1.13. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(6-hydroxynaphthalen-1-yl)propene,
6b. Prepared following the method for 6a. Yield 0.03 g
(51%). 200 MHz 1H NMR (acetone-d6) d 6.46–8.00
(m, 14H, ArH); 3.85–4.09 (t, 2H, OCH2); 2.72 (t, 2H,
NCH2); 2.50 (m, 4H, CH2NCH2); 1.82–2.21 (s, 3H,
CH3); 1.53 (m, 4H, CH2CH2NCH2CH2); 1.44 (m, 2H,
NCH2CH2CH2).
5.1.8. (E/Z)-1-(4-Methoxyphenyl)-2-(4-(2-piperidin-1-yl)-
ethoxy)phenyl-1-(5-methoxynaphthalen-1-yl)propene, 5c.
Prepared following the method for 5a using 4b and 1-
iodo-5-methoxynaphthalene (see method for 1-iodo-6-
methoxynaphthalene12). Yield 0.142 g (52%). 200 MHz
1H NMR (CDCl3) d 6.50–8.27 (m, 14H, ArH); 4.11 (t,
2H, OCH2); 3.67–4.02 (s, 6H, OCH3); 2.80 (t, 2H,
NCH2); 2.56 (m, 4H, CH2NCH2); 1.85 (s, 3H, CH3);
1.64 (m, 4H, CH2CH2NCH2CH2); 1.49 (m, 2H,
NCH2CH2CH2).
5.1.14. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(5-hydroxynaphthalen-1-yl)propene,
6c. Prepared following the method for 6a. Yield 0.06 g
(45%). 400 MHz 1H NMR (acetone-d6) d 6.38–8.07
(m, 14H, ArH); 3.75–4.01 (t, 2H, OCH2); 2.50–2.62 (t,
2H, NCH2); 2.41 (m, 4H, CH2NCH2); 1.73 (s, 3H,
CH3); 1.47 (m, 4H, CH2CH2NCH2CH2); 1.34 (m, 2H,
NCH2CH2CH2).
5.1.9. (E/Z)-1-(4-Methoxyphenyl)-2-(4-(2-piperidin-1-yl)-
ethoxy)phenyl-1-(6-methoxynaphthalen-2-yl)butene, 5d.
Prepared following the method for 5a using 4c and 2-
bromo-6-methoxynaphthalene. Yield 0.263 g (91%).
200 MHz 1H NMR (CDCl3) d 6.52–7.76 (m, 14H,
ArH); 3.95–4.13 (t, 2H, OCH2); 3.68–3.93 (s, 6H,
OCH3); 2.65–2.80 (t, 2H, NCH2); 2.47 (m, 6H,
CH2NCH2 + CH2); 1.60 (m, 4H, CH2CH2NCH2CH2);
1.45 (m, 2H, NCH2CH2CH2); 0.97 (t, 3H, CH3).
5.1.15. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(6-hydroxynaphthalen-2-yl)butene, 6d.
Prepared following the method for 6a. Yield 0.124 g
(51%). 400 MHz 1H NMR (methanol-d4) d 6.41–7.65
(m, 14H, ArH); 3.97–4.05 (t, 2H, OCH2); 2.65–2.75 (t,
2H, NCH2); 2.40–2.58 (m, 4H, CH2NCH2 + CH2);
1.55 (m, 4H, CH2CH2NCH2CH2); 1.43 (m, 2H,
NCH2CH2CH2); 0.90 (m, 3H, CH3).
5.1.10. (E/Z)-1-(4-Methoxyphenyl)-2-(4-(2-piperidin-1-yl)-
ethoxy)phenyl-1-(6-methoxynaphthalen-1-yl)butene, 5e.
Prepared following the method for 5a using 4c and
1-iodo-6-methoxynaphthalene. Yield 0.185 g (85%).
200 MHz 1H NMR (CDCl3) d 6.50–7.99 (m, 14H,
ArH); 4.10 (t, 2H, OCH2); 3.66–3.92 (s, 6H, OCH3);
2.79 (t, 2H, NCH2); 2.53 (m, 4H, CH2NCH2); 2.20 (q,
2H, CH2); 1.62 (m, 4H, CH2CH2NCH2CH2); 1.46 (m,
2H, NCH2CH2CH2); 0.77 (t, 3H, CH3).
5.1.16. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(6-hydroxynaphthalen-1-yl)butene, 6e.
Prepared following the method for 6a. Yield 0.124 g
(51%). 400 MHz 1H NMR (methanol-d4) d 6.31–7.83
(m, 14H, ArH); 3.99 (t, 2H, OCH2); 2.69 (t, 2H,
NCH2); 2.47 (m, 4H, CH2NCH2); 2.07 (m, 2H, CH2);
1.54 (m, 4H, CH2CH2NCH2CH2); 1.40 (m, 2H,
NCH2CH2CH2); 0.66 (m, 3H, CH3).
5.1.11. (E/Z)-1-(4-Methoxyphenyl)-2-(4-(2-piperidin-1-yl)-
ethoxy)phenyl-1-(5-methoxynaphthalen-2-yl)butene, 5f.
Prepared following the method for 5a using 4c and
1-iodo-5-methoxynaphthalene. Yield 0.238 g (83%).
200 MHz 1H NMR (CDCl3) d 6.48–8.25 (m, 14H,
ArH); 4.09 (t, 2H, OCH2); 3.64–4.00 (s, 6H, OCH3);
5.1.17. (E/Z)-1-(4-Hydroxyphenyl)-2-(4-(2-piperidin-1-
yl)ethoxy)phenyl-1-(5-hydroxynaphthalen-1-yl)butene, 6f.
Prepared following the method for 6a. Yield 0.111 g
(69%). 400 MHz H NMR (DMSO-d6) d 10.04 (s, 1H,
OH); 9.08 (s, 1H, OH); 6.28–8.23 (m, 14H, ArH); 3.94
(t, 2H, OCH2); 2.57 (t, 2H, NCH2); 2.35 (m, 4H,
1