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3 : 1 : 0.01) to give 6 as a light yellow amorphous solid (2.8819
g, yield: 96%). 6a: H NMR (400 MHz, CDCl3) d = 8.51 (dd, J =
Synthesis of compound 14. A suspension of enone 11
(0.3193 g, 1.251 mmol) and Pd/C (10%, 0.3512 g) in ethyl
acetate (25 mL) was stirred under a hydrogen atmosphere at rt
for 3 h. After the catalyst was removed by filtration, the filtrate
was concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel
(EA : PET : Et3N = 3 : 1 : 0.01) to give 14 as a white solid
(0.2929 g, yield: 91%); mp 125–126 uC; 1H NMR (400 MHz,
CDCl3) d = 8.50 (dd, J = 1.6, 4.8 Hz, 1H), 8.36 (d, J = 1.6 Hz, 1H),
7.37 (dt, J = 1.6, 8.0 Hz, 1H), 7.22 (dd, J = 4.8, 7.6 Hz, 1H), 3.18
(d, J = 14.0 Hz, 1H), 3.04 (d, J = 14.4 Hz, 1H), 2.99 (d, J = 18.4
Hz, 1H), 2.69 (m, 1 H), 2.55–2.43 (m, 2H), 2.29–2.19 (m, 2H),
2.11–1.87 (m, 4H), 1.10 (d, J = 6.4 Hz, 3H) ppm; 13C NMR (125
MHz, CDCl3) d = 213.88, 211.22, 150.46, 148.71, 136.86, 131.83,
123.40, 56.82, 46.49, 44.76, 42.88, 41.34, 38.88, 31.81, 30.07,
21.98 ppm; HRMS (ESI) calcd. for C16H19NO2H+ [M + H+]
258.1489, found 258.1486.
1
1.6, 4.8 Hz, 1H), 8.26 (d, J = 1.6 Hz, 1H), 7.28 (dt, J = 1.6, 8.0 Hz,
1H), 7.20 (dd, J = 4.8, 8.0 Hz, 1H), 2.92 (s, 2H), 3.26 (s, 2H),
2.57–2.44 (m, 4H), 2.04 (s, 3H), 1.27 (m, 1H), 0.95 (d, J = 6.5 Hz,
3H) ppm; 13C NMR (125 MHz, CDCl3) d = 210.95, 206.18,
150.72, 149.02, 137.26, 130.97, 123.36, 62.59, 52.54, 46.58,
40.15, 28.77, 23.01, 21.37 ppm; HRMS (ESI) calcd. for
C16H19NO3H+ [M + H+] 274.1438, found 274.1434. 6b: 1H
NMR (400 MHz, CD3OD) d = 8.43 (dd, J = 1.6, 4.8 Hz, 1H), 8.24
(d, J = 1.6 Hz, 1H), 7.55 (dt, J = 1.6, 7.9 Hz, 1H), 7.37 (dd, J = 4.8,
7.8 Hz, 1H), 3.15 (s, 2H), 3.02 (s, 2H), 2.63–2.61 (m, 4H), 2.42
(m, 1H), 2.02 (s, 3H), 1.14 (d, J = 6.4 Hz, 3H) ppm; 13C NMR
(125 MHz, CD3OD) d = 210.59, 208.24, 151.30, 148.99, 130.98,
133.12, 124.93, 65.15, 48.73, 47.93, 39.70, 28.85, 26.65, 21.77
ppm; HRMS (ESI) calcd. for C16H19NO3H+ [M + H+] 274.1438,
found 274.1437.
Synthesis of compound 11. A mixture of triketone 6 (0.8960
g, 3.278 mmol), KF?2H2O (0.9257 g, 9.834 mmol) and 18-
crown-6 (0.4072 g, 1.541 mmol) in 50 mL of benzene was
heated under refluxing for 3 h with continuous removal of
water using a Dean–Stark trap filled with Linde 4 Å molecular
sieves. After that, the solvent was removed and xylene (60 mL)
was added. Refluxing was further continued for 16 h. The
solvent was removed at reduced pressure. The residue was
dissolved in EA (30 mL), washed with brine (3 6 2 mL), dried
over anhydrous Na2SO4, filtered and concentrated. The residue
was purified by column chromatography on silica gel
(EA : PET : Et3N = 3 : 1 : 0.01) to give 11 as a white amorphous
solid (0.3530 g, yield: 42%), 12 as an oil (0.0363 g, yield: 4%)
and 13 as a pale yellow oil which is an inseparable mixture of
epimers. 11: 1H NMR (400 MHz, CDCl3) d = 8.50 (dd, J = 1.6, 4.8
Hz, 1H), 8.31 (d, J = 1.6 Hz, 1H), 7.36 (dt, J = 1.6, 7.6 Hz, 1H),
7.20 (dd, J = 4.8, 7.6 Hz, 1H), 5.84 (d, J = 1.6 Hz, 1H), 3.12 (d, J =
1.2 Hz, 2H), 3.12–3.00 (m, 1H), 2.99 (d, J = 18.8 Hz, 1H), 2.69–
2.57 (m, 3H), 2.22 (d, J = 18.8 Hz, 1H), 2.04 (m, 1H), 1.26 (d, J =
6.4 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3) d = 207.36,
204.76, 177.54, 150.67, 149.01, 136.94, 130.28, 129.82, 123.33,
62.44, 46.18, 40.54, 39.72, 35.60, 33.95, 22.19 ppm; HRMS (ESI)
calcd. for C16H17NO2H+ [M + H+] 256.1332, found 256.1330. 12:
1H NMR (400 MHz, CDCl3) d = 8.46 (dd, J = 1.6, 4.8 Hz, 1H),
8.29 (d, J = 1.6 Hz, 1H), 7.34 (dt, J = 1.6, 7.6 Hz, 1H), 7.17 (dd, J
= 4.8, 7.6 Hz, 1H), 5.85 (d, J = 1.6 Hz, 1H), 3.18–3.07 (m, 4H),
2.95 (d, J = 18.8 Hz, 1H), 2.72 (m, 2H), 2.34 (dt, J = 2.4, 19.2 Hz,
Synthesis of compound 5. To a solution of 14 (0.1 g, 0.389
mmol) in acetone (5 mL) was added methyl iodide (0.1655 g,
1.166 mmol). The reaction was heated under reflux for 3 h,
then removal of the solvent gave 5 as a pale yellow amorphous
solid (0.1552 g, 100%): 1H NMR (400 MHz, (CD3)2SO) d = 8.88–
8.86 (m, 2H), 8.28 (d, J = 8.0 Hz, 1H), 8.04 (t, J = 7.6 Hz, 1H),
4.32 (s, 3H), 3.63 (d, J = 13.6 Hz, 1H), 3.22 (d, J = 14.0 Hz, 1H),
2.87–2.76 (m, 2H), 2.61 (d, J = 18.0 Hz, 1H), 2.26–1.99 (m, 6H),
1.77 (d, J = 13.2, 1H), 1.06 (d, J = 6.0 Hz, 3H) ppm; 13C NMR
(125 MHz, (CD3)2SO) d = 214.25, 211.86, 145.43, 145.14, 143.98,
137.84, 127.11, 56.36, 47.94, 46.02, 44.43, 43.23, 40.83, 36.98,
30.61, 29.35, 21.63 ppm; HRMS (ESI) calcd. for C17H22NO2+ [M
2 I2] 272.1645, found 272.1644.
Synthesis of compound 15. To a vigorously stirred suspen-
sion of 5 (0.15 g, 0.376 mmol) in toluene (40 mL) was added 4
N aqueous NaOH (0.75 mL, 3.005 mmol) at rt. The reaction
mixture was stirred until the solid was dissolved completely.
The organic phase was separated, and the aqueous phase was
extracted with toluene (2 6 10 mL). The combined organic
layers were dried over Na2SO4 for 10 min and filtered. The
filtrate was treated with a solution of iodine (0.1430 g, 0.564
mmol) in toluene (5 mL) immediately at rt. After stirring for 10
h, to the reaction mixture was added saturated aqueous
Na2SO3 until a colorless mixture was obtained. The reaction
mixture was concentrated to dryness. The resulting solid was
suspended in methanol (10 mL) and cooled to 210 uC. To the
above mixture was added NaBH4 (0.0213 g, 0.564 mmol). The
reaction mixture was stirred for 20 min at 210 uC, quenched
with 1 N aqueous HCl and basified with saturated aqueous
NaHCO3. Methanol was removed under reduced pressure and
the aqueous layer was extracted with chloroform (4 6 5 mL).
The extracts were dried over Na2SO4, filtered and concentrated.
The residue was dissolved in acetone (5 mL) and cooled to 0
uC. Jones reagent was added to the above solution until the
persistence of the orange color. Stirring was continued for an
additional 2 h. The reaction was quenched with isopropanol,
basified with saturated aqueous NaHCO3 and concentrated.
The resulting aqueous layer was extracted with CH2Cl2 (4 6 5
mL). The extracts were dried over anhydrous Na2SO4, filtered
and concentrated. The residue was purified by column
chromatography on silica gel (CH2Cl2 : MeOH = 10 : 1) to give
1H), 2.20 (d, J = 18.8 Hz, 1H), 0.89 (d, J = 6.8 Hz, 3H) ppm; 13
C
NMR (100 MHz, CDCl3) d = 208.08, 204.04, 176.69, 150.72,
148.94, 136.87, 132.13, 130.40, 123.21, 63.35, 44.49, 40.83,
39.72, 33.62, 30.05, 19.38 ppm; HRMS (ESI) calcd. for
C16H17NO2H+ [M + H+] 256.1332, found 256.1330. 13: 1H
NMR (400 MHz, CDCl3) d = 11.27 (br, 1H), 8.43–8.37 (m, 2H),
7.57–7.55 (m, 1H), 7.26–7.22 (m, 1H), 3.11–3.04 (m, 1H), 2.82–
2.74 (m, 1H), 2.70–2.50 (m, 4H), 2.15 (s, 0.54H), 2.10 (s, 0.42H),
1.99 (s, 3H), 1.19 (d, J = 6.8 Hz, 1.7H), 1.15 (d, J = 7.2 Hz, 1.2H)
ppm; 13C NMR (100 MHz, CDCl3) d = 208.97, 176.16, 175.90,
169.40, 169.30, 149.22, 149.02, 146.83, 146.62, 141.67, 141.56,
137.40, 137.23, 135.38, 135.29, 123.65, 123.52, 45.65, 45.61,
38.43, 38.34, 37.68, 37.55, 34.48, 33.92, 33.88, 27.35, 27.24,
18.45, 18.29, 17.13 ppm; HRMS (ESI) calcd. for C16H19NO3H+
[M + H+] 274.1438, found 274.1436.
11018 | RSC Adv., 2013, 3, 11014–11020
This journal is ß The Royal Society of Chemistry 2013