SYNTHESIS OF TRITIUM LABELLED L783483
463
1
3
1
.73 (m, 2 H), 0.98 (t, 3 H). C NMR (DMSO-d ) d 163.5, 155.5, 148.5
6
(
q, J¼ 38:3 Hz), 121.8, 120.5, 119.6 (q, J¼ 271:8 Hz), 116.4, 113.7, 71.9,
+
2.6, 30.9, 26.4, 22.1, 13.9. MS: M =443.
3
3
5- H]-6-(3-Bromopropyloxy)-7-propyl-3-trifluoromethyl-benzisoxazole
[
(4b). Compound 3 (3.8 mg, 8.5 mmol) was dissolved in ethanol (0.5 ml),
1
0% Pd on carbon (2.0 mg) was added and the mixture was treated with
tritium gas for 30 min.Volatile tritium compounds were removed by
lyophilisation with methanol (3 ꢀ 1 ml). Catalyst was removed by
filtration and the filtrate was concentrated in vacuo. The residue was
applied to a 20 ꢀ 20 ꢀ 0.05 (cm) silica gel TLC plate and eluted with n-
hexane/ethyl acetate 4:1 (v/v). The strongest UV-band (254 nm) (Rf
0
.43) containing compound 4b was eluted with ethyl acetate, followed
by removal of solvent in vacuo. The residue was chromatographed on a
Merck Lichrosper RP-18 250-10 column with acetonitrile/0.05 M
phosphoric acid 73:27 (v/v) (4 ml/min, UV-detection at 254 nm) as
eluent. The fraction from 28.3–32.3 min was collected, neutralized with
2
M sodium hydroxide (0.10 ml) and concentrated to a volume of
approximately 4 ml.The remaining aqueous phase was extracted with
ethyl acetate (3 ꢀ 2 ml). Drying over sodium sulphate, filtration and
evaporation of solvent in vacuo gave [5- H]-6-(3-bromopropyloxy)-7-
3
propyl-3-trifluoromethyl-benzisoxazole (4b), which was dissolved in
ethanol (5.00 ml). The analysis of this solution showed a total
radioactivity of 2990 MBq and a radiochemical purity of 99%. For
use in the following reaction ethanol was removed in vacuo, and
compound 4b was transferred to a 1 ml vial with ethyl acetate followed
by removal of solvent in a gentle stream of argon. Unlabelled 6-(3-
2
bromopropyloxy)-7-propyl-3-trifluoromethyl-benzisoxazole (4a) - used
1
as a reference compound - had the following spectroscopic data: H
NMR (DMSO-d ) d 7.76 (d, 1 H), 7.39 (d, 1 H), 4.29 (t, 2 H), 3.72
6
1
3
(t, 2 H), 2.87 (m, 2 H), 2.34 (m, 2 H), 1.65 (m, 2 H), 0.91 (t, 3 H).
C
NMR (DMSO-d ) d 164.0, 158.9, 149.0 (q, J¼ 37:8 Hz), 120.1 (q,
6
J¼ 271:3 Hz), 119.0, 112.9, 112.1, 109.9, 67.0, 31.8, 31.0, 25.0, 21.7,
+
3.8. MS: M =465.
1
3
-Chloro-4-(3-(7-propyl-3-trifluoromethyl-[5- H]-benzisoxazol-6-oxy)-
3
2
propylsulphanyl)phenylacetic acid (5b) (cf. reference ). 3-Chloro-4-
4
(
dimethylaminocarbonylsulphanyl)-phenylacetic acid methyl ester
6.4 mg, 0.022 mmol) was stirred under argon with a solution of 0.5 M
(
sodium methoxide in methanol (60 ml, 0.030 mmol) at 638C for
Copyright # 2003 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2003; 46: 459–464