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Synthesis of 1,8-ditosyloctane 12: In a 150 ml round bottom flask, 1,8-
octanediol (6.66 g, 45.6 mmol) was dissolved in 50 ml of pyridine; the solution
was cooled to 08C and then tosyl chloride (26.8 g, 140.6 mmol) was added. The
mixture was stirred at 08C for 30 min and then stored in a refrigerator
overnight. The solution was then poured into ice water and the white solid
precipitate filtered and dried affording 13.6 g of pure product (66% yield based
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on the diol). MS (FAB+) m=z: 455. H-NMR (CDCl3): (d ppm, J Hz) 7.79
(4H, d, 8.2), 7.35 (4H, d, 8.2), 4.01 (4H, t, 6.8), 2.46 (6H, s), 1.61 (6H, b), 1.21
(6H, bm); 13C-NMR (CDCl3): 144.8, 133.2, 130.0, 128.0, 70.7, 28.8, 28.7,
25.2, 21.7.
Synthesis of 2-(8-tosyloctyloxy)-naphthalene 13: In a 10 ml round flask,
b-naphthol (0.130 g, 0.9 mmol) was dissolved in 4 ml of CH3CN and 1 ml of
1.52 M Bu4NOH was added as base; compound 12 (0.520 g, 1.52 mmol),
dissolved in 4 ml of CH3CN, was added to the solution in five portions. The
solution was stirred overnight at room temperature. A white precipitate
formed that was identified as the undesired product resulting from
dimerization of two naphthol unit through the octyl bridge. Hence, the
solution was filtered, the filtrated concentrated and purified using flash
chromatography (75/20/5=Hexane/CHCl3/EtOAc, Rf ¼ 0:43) obtaining
0.163 g (0.38 mmol) of a yellow oil (42% yield). This compound was
crystallized from cold CH3CN containing a few drops of water yielding pale
yellow crystals. MS (FAB+) m=z: 427. 1H-NMR (CDCl3): (d ppm, J Hz) 7.76
(5H, m), 7.33 (4H, m), 7.13 (2H, m), 4.04 (4H, dd, 6.4, 12.8), 2.44 (3H, s), 1.82
(2H, m), 1.64 (2H, m), 1.30 (8H, b); 13C-NMR (CDCl3): 157.2, 144.8, 134.8,
133.5, 130.0, 129.5, 129.1, 128.1, 127.8, 126.9, 126.5, 123.7, 119.2, 106.8, 70.8,
68.1, 29.4, 29.2, 26.2, 25.5, 21.8.
Synthesis of 2-(8-iodooctyloxy)-naphthalene 11: Compound 13 (0.148 g,
0.35 mmol) was placed in a 25 ml round bottom reaction flask and dissolved in
10 ml of acetone; NaI (0.065 g, 0.43 mmol) was added. The solution was heated
under gentle reflux with magnetic stirring overnight. The solvent was
evaporated and the residue partitioned between CH2Cl2/H2O; the evaporation
of the organic solvent gives 0.041 g (31% yield) of 11. GC-MS: 93% purity;
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m=z: 382, 157, 144, 127, 115, 69. H-NMR (CDCl3): (d ppm, J Hz) 7.73 (3H,
m), 7.35 (2H, m), 7.16 (2H, m), 4.07 (2H, t, 6.4), 3.19 (2H, t, 6.8), 1.84 (4H, m),
1.38 (8H, b); 13C-NMR (CDCl3): 157.3, 134.8, 129.5, 129.1, 127.8, 126.9,
126.5, 123.7, 119.2, 106.8, 68.1, 33.7, 30.6, 29.4, 28.7, 26.24.
Synthesis of 2-(8-fluorooctyloxy)-naphthalene F-11: Compound 13 (0.163 g,
0.38 mmol) was placed in a 25 ml round bottom reaction flask and dissolved in
5 ml of acetonitrile; Me4NHF2 (0.170 g, 1.5 mmol) was added. The solution
was heated to reflux under magnetic stirring for 2 h. The solvent was
evaporated and the residue partitioned between CH2Cl2/H2O. Evaporation of
the organic solvent gives 0.057 g (55% yield) of F-11. GC-MS: >99% purity;
Copyright # 2004 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2004; 47: 373–383