ORDER
REPRINTS
5-HT2C RECEPTOR AGONIST, ORG 37684
2033
was stirred at 15ꢀC for 1 h then allowed to warm to room temperature and
stirred for a further 2 h. The mixture was poured into ice/water (1.2 l) and
extracted with diethyl ether (3Â200 ml). The combined organic extracts were
dried (MgSO4), filtered and concentrated in vacuo to leave a brown oil. The
oil was purified by chromatography on silica gel using ethyl acetate/hexane
(1:24) as eluent to give the product (26.4 g, 57%) as a white solid. Mp
68–70ꢀC; ꢀmax (nujol) 3406, 2927, 2855, 1494, 1459, 1444, 1377, 1354,
1423, 1304, 1285, 1234, 1148, 1076, 1000, 914, 894, 790, 725, and 546 cmꢁ1
.
dH (400 MHz: CDCl3) 6.69 (1H, d, J ¼ 8 Hz, Ar-H), 6.66 (1H, d, J ¼ 8 Hz,
Ar-H), 5.59 (1H, br. s, OH), 3.85 (3H, s, OCH3), 2.89 (2H, app. t,
J ¼ 7.2 Hz, ArCH2), 2.84 (2H, app. t, J ¼7.5 Hz, ArCH2), 2.08 (2H, m,
ArCH2CH2); Found C, 73.11; H, 7.40; C10H12O2 requires C, 73.15; H,
7.40%. Further elution with ethyl acetate/hexane (1:24) gave 4-methoxy-
5-indanol 9 (1.1 g, 2%) as a yellow oil. ꢀmax (film) 3425, 2945, 2845, 1850,
1729, 1611, 1483, 1460, 1437, 1351, 1288, 1268, 1229, 1194, 1161, 1042, 1006,
969, 936, 906, 811, 742 and 673 cmꢁ1. dH (400 MHz; CDCl3) 6.81 (1H, d,
J ¼ 8 Hz, Ar-H), 6.73 (1H, d, J ¼ 8 Hz, Ar-H), 5.56 (1H, br, s, OH), 3.86
(3H, s, OCH3), 2.95 (2H, app. t, J ¼ 7.5 Hz, ArCH2), 2.79 (2H, app. t,
J ¼ 7.5 Hz, ArCH2), 2.04–2.11 (2H, m, ArCH2CH2). Further elution with
ethyl acetate/hexane (3:7) gave 4,5-dihydroxyindan 8 (9 g, 21%) as a yellow
oil. vmax (nujol) 3318, 2925, 2853, 1632, 1595, 1508, 1479, 1466, 1438, 1377,
1338, 1311, 1279, 1234, 1197, 1141, 1009, 940, 904, 780, 760, 723 and
686 cmꢁ1; dH (400 MHz; CDCl3) 6.63–6.67 (2H, m, 2 Â Ar-H ), 5.20 (2H,
br, s, 2 Â OH), 2.81 (4H, app. t, J ¼ 7.5 Hz, 2 Â ArCH2), 2.04–2.11 (2H, m,
ArCH2CH2).
(3R)-1-Benzyl-3-methanesulfonyloxy pyrrolidine 10: Methanesulfonyl
chloride (11.6 ml, 149 mmol) was added dropwise over 30 min to a stirred
solution of (3R)-1-benzyl-3-pyrrolidinol (22 g, 120 mmol) and triethylamine
(26.1 ml, 186 mmol) in dichloromethane (200 ml) at 0ꢀC under argon.
The mixture was stirred at 0ꢀC for a further 3 h. The solvent was removed
in vacuo to leave a crude residue. The residue was partitioned between water
(200 ml) and diethyl ether (200 ml) and the aqueous layer was re-extracted
with diethyl ether (2 Â 100 ml). The combined organic extracts were washed
with brine (1Â100 ml), dried (MgSO4), filtered and concentrated in vacuo
to leave the product (27.7 g, 100%) as a yellow oil. ꢀmax (film) 3028, 2940,
2799, 1959, 1734, 1604, 1586, 1496, 1479, 1454, 1416, 1354, 1249, 1171, 1146,
1075, 1028, 958, 895, 851, 796, 743, 702, 630, 534, 524 and
466 cmꢁ1; dH (400 MHz; CDCl3) 7.26–7.32 (5H, m, 5 Â Ar-H), 5.17–5.21
(1H, m, CHOSO2CH3), 3.67 (1H, d, J ¼ 12.5 Hz, NCH HPh), 3.61 (1H, d,
J ¼ 12.5 Hz, NCHHPh), 2.99 (3H, s, OSO2CH3), 2.73–2.92 (3H, m,
NCH2 þ NCH H), 2.48–2.54 (1H, m, NCH H), 2.27–2.36 (1H, m,
NCH2CH H), 2.05–2.12 (1H, m, NCH2CH H).