174 A. LEWIN ET AL.
Scheme 4
These observations led to the development of a protocol
(Scheme 4) in which DBTC (2) was reacted with two
equivalents of butyl bromide (9) and excess lithium,
without sonication, to furnish tetrabutyltin (3) in high
yield and satisfactory purity.
(m, 2H, CH3-CH2); 1.74 (m, 2H, CH2-CH2-CH2O);
3.01, (s, 3H, SCH3); 4.22 (t, 2H, CH2O).
[
14C]butyl bromide [14C]-9
A mixture of [14C]-10 (96 mCi, 1.69 mmol) and tetra-
butylammonium bromide (700 mg, 2.17 mmol) in isooc-
tane (5 ml) was heated under reflux in a N2 atmosphere
for 2h. The mixture was cooled to 08C and the isooctane
carefully removed. The remaining suspension was di-
luted with isooctane (3 ml) and the mixture was refluxed
for an additional 2 h. The suspension was cooled to 08C,
the isooctane phase carefully siphoned from the pre-
cipitated salts and the organic solution combined with
the first extract. This solution contained 87 mCi (90%
yield) of [14C]-9. Because of its highly volatile nature the
product was used directly in the next synthesis step.
With this information in hand the radiosynthesis was
undertaken. The preparation of [14C]-butanol ([14C]-8)
was carried out as shown in Scheme 3 (77%). Conver-
sion to butyl bromide ([14C]-9) (Scheme 3), followed by
treatment with DBTC (2) (Scheme 4) furnished [14C]-3
in 55% yield. Fusion of [14C]-3 with equimolar tin
tetrachloride in the presence of aluminum trichloride
as catalyst gave
[
14C]DBTC ([14C]-2) in >98%
radiochemical purity and 30% overall yield from
Ba14CO3.
Experimental
[
14C]tetrabutyltin [14C]-3
Proton magnetic resonance spectra were obtained on a
Bruker Avance 300 spectrometer. Decolorizing carbon
Norit N (Fisher Scientific Co) was activated by heating
in vacuo at 2508C for 10 min. Radioactive samples were
counted using a Packard Tri-carb 2100 TR liquid
scintillation spectrometer in Packard Utlima Gold
cocktail using the external standard channels ratio as
a method of quench correction.
To a solution of [14C]-9 (87 mCi, 1.52 mmol) in THF
(95 ml) at 08C was added SnCl4 (215 mg, 0.827 mmol)
and hexane-washed lithium (30 mg, 4.29 mmol). The
suspension was stirred at 08C for 15 min, then at 258C
for 30 min. The mixture was cooled to 08C and small
chips of ice were added followed by 1 N HCl to pH1. The
organic phase was isolated, the aqueous layer re-
extracted with isooctane, (2 ml) and the combined
organic phase was concentrated to ꢀ1 ml. The residue
was cooled to À208C overnight and a small amount of
precipitate that formed was removed by filtration. The
filtrate contained 63 mCi (72% yield) of [14C]-3; 1H NMR
analysis of an aliquot indicated the product was of
adequate purity. 1H NMR (CDCl3) d (ppm): 0.80 (t, 8H,
CH2Sn); 0.89 (t, 12H, CH3); 1.28 (m, 8H, CH2CH2Sn);
1.47 (m, 8H, CH2CH3). The isooctane extract was
evaporated to a colorless oil that was used for the
preparation of the target compound.
[
14C]butyl mesylate [14C]-10
[
14C]Butanol 14C]-811 (115 mCi, 2.03 mmol) was
[
cooled to 08C, and triethylamine (650 mg, 6.43 mmol)
followed by mesyl chloride (550 mg, 2.03 mmol) were
added with stirring at 08C. After a few minutes a white
precipitate began to separate. The mixture was allowed
to come to ambient temperature and stirring was
1
2
continued 1 h. The product was concentrated to the
volume and the solution was cooled to À28C overnight.
The supernatant was carefully siphoned from a white
solid, then water was added to the residue and the
product was extracted with isooctane (2 Â 2 ml). The
combined organic extract was evaporated to a colorless
oil (288 mg, 96 mCi, 83% yield) which based on 1H NMR
analysis was of adequate purity for further synthesis.
1H-NMR (CDCl3) d (ppm): 0.96 (t, 3H, CH3); 1.40
[
14C]dibutyltin dichloride [14C]-2
In a Teflon sealed vial a mixture of [14C]tetrabutyltin
14C]-3 (178 mg, 0.5 mmol), SnCl4 (176mg, 0.677 mmol)
[
and AlCl3 (20mg, 0.150 mmol) was heated at 115–1258C
for 3–4 h under an atmosphere of argon. The cooled oil
Copyright # 2007 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2007; 50: 171–175
DOI: 10.1002.jlcr