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2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
PPh -CCl CN System
3
2889
3
reaction mixture was then treated with DL-a-tocopherol (1b) (862 mg,
2
.0 mmol) followed by DMAP (733 mg, 6.0 mmol). The reaction mixture
ꢀ
was allowed to react for 2 h at 75 C. The reaction mixture was then con-
centrated under vacuum. The reaction mixture was washed with water.
The organic layer was dried over anhydrous MgSO . Afterfilt ar tion,
4
the solvent was removed and the residue was purified with column chro-
matography on silica gel (n-hexane:EtOAc, 2:1) to give DL-a-tocopherol
ꢀ
[13]
ꢀ
nicotinate (1c) (900 mg, 84%): M.p. 37–38 C (Lit.
1
32 C);
H NMR ꢀ (CDCl , 300 MHz) ꢀ 0.83–0.88 (m, 15H), 2.02 (s, 3H), 2.06
3
(
1
1
s, 3H), 2.12 (s, 3H), 2.63 (t, J ¼ 6.6 Hz), 7.48 (dd, J ¼ 5.1 Hz, J ¼ 8.0 Hz,
H), 8.49 (d, J ¼ 8.1 Hz, 1H), 8.86 (d, J ¼ 5.1 Hz, 1H), 9.45 (s, 1H);
3
C NMR (CDCl , 75 MHz) ꢀ 11.9, 12.1, 13.9, 19.8, 19.9, 21.3, 21.6,
3
2
4
1
2.7, 24.8, 25.2, 25.2, 28.6, 32.6, 33.0, 33.1, 37.5, 37.7, 37.8, 37.9, 39.7,
1.5, 75.1, 120.2, 123.1, 123.5, 124.4, 125.4, 130.6, 136.8, 144.8, 146.3,
51.4, 152.5, 167.7.
Synthesis of flavoxate (2c). Flavoxate (2c) was prepared according to
the typical procedure with 3-methylflavone-8-carboxylic acid (2a)
560 mg, 2.0 mmol) and 1-(2-hydroxyethyl)piperidine (2b) (0.27 mL,
.0 mmol). The product was purified with column chromatography on
silica gel (n-hexane:EtOAc, 2:1) to give 572 mg (73%) of flavoxate (2c):
(
2
ꢀ
[12]
ꢀ
1
M.p. 87–88 C (Lit. 85–86 C); H NMR (CDCl , 300 MHz) ꢀ 1.37–1.57
3
(
m, 6H), 2.10 (s, 3H), 2.38 (m, 4H), 2.43 (t, J ¼ 5.4 Hz, 2H), 3.55 (t,
J ¼ 5.4 Hz, 2H), 7.56 (m, 4H), 7.81 (m, 2H), 8.19 (d, J ¼ 7.8 Hz, 1H),
1
3
8
5
1
.26 (d, J ¼ 8.2 Hz, 1H); C NMR (CDCl , 75 MHz) ꢀ 8.9, 25.1, 26.4,
3
5.5, 57.9, 62.3, 112.2, 114.4, 121.5, 125.4, 128.8, 128.8, 129.0, 129.3,
23.0, 135.3, 158.7, 162.1, 165.4, 176.6.
Synthesis of clofibrate (3c). Clofibrate (3c) was prepared according to
the typical procedure with clofibric acid (3a) (860 mg, 4.0 mmol) and
ethanol (0.47 mL, 8.0 mmol). The product was purified with column chro-
matography on silica gel (n-hexane:EtOAc, 2:1) to give 752 mg (78%) of
ꢀ
[11]
ꢀ
clofibrate (3c): b.p. 148–150 C/20 mmHg (Lit.
1
80–84 C/0.1 mmHg);
H NMR (CDCl , 300 MHz) ꢀ 1.34 (t, J ¼ 7.1 Hz, 3H), 1.59 (s, 6H),
3
4
2
.23 (q, J ¼ 6.6 Hz, 2H), 6.79 (d, J ¼ 8.9 Hz, 2H), 7.19 (d, J ¼ 8.9 Hz,
1
3
H); C NMR (CDCl , 75 MHz) ꢀ 14.4, 24.9, 61.5, 78.7, 115.9, 128.3,
3
136.6, 155.6, 170.3.
ACKNOWLEDGMENTS
This work was supported by Maeji Institute of Academic Research,
Yonsei University.