U.S. patent application number 12/651494 was filed with the patent office on 2010-04-29 for radiosynthesis of acid chlorides.
This patent application is currently assigned to Hammersmith Imanet Limited. Invention is credited to Edward Robins, DAVID ROBERT TURTON.
Application Number | 20100105949 12/651494 |
Document ID | / |
Family ID | 32118089 |
Filed Date | 2010-04-29 |
United States Patent
Application |
20100105949 |
Kind Code |
A1 |
TURTON; DAVID ROBERT ; et
al. |
April 29, 2010 |
RADIOSYNTHESIS OF ACID CHLORIDES
Abstract
Radiolabelled acid chlorides may be synthesised by reacting a
radiolabelled carboxylic acid with a solid-phase supported
chlorinating agent.
Inventors: |
TURTON; DAVID ROBERT;
(London, GB) ; Robins; Edward; (London,
GB) |
Correspondence
Address: |
GE HEALTHCARE, INC.
IP DEPARTMENT 101 CARNEGIE CENTER
PRINCETON
NJ
08540-6231
US
|
Assignee: |
Hammersmith Imanet Limited
|
Family ID: |
32118089 |
Appl. No.: |
12/651494 |
Filed: |
January 4, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10599117 |
Jul 20, 2007 |
7642375 |
|
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PCT/GB2005/001137 |
Mar 18, 2005 |
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12651494 |
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Current U.S.
Class: |
562/840 |
Current CPC
Class: |
C07B 59/001
20130101 |
Class at
Publication: |
562/840 |
International
Class: |
C07C 53/00 20060101
C07C053/00 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 20, 2004 |
GB |
0406315.2 |
Claims
1-24. (canceled)
25. A kit for carrying out a method for the preparation of a
radiolabelled acid chloride compound of formula (I): R--COCl (I)
wherein R is C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl,
C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocyclyl,
C.sub.4-C.sub.10 aryl or C.sub.4-C.sub.10 heteroaryl, any of which
may optionally be substituted with NO.sub.2, --O(C.sub.1-C.sub.6
alkyl), C.sub.3-C.sub.10 cycloalkyl or C.sub.4-C.sub.10 aryl; the
method comprising reacting a radiolabelled carboxylic acid of
formula (II): R--COOH (II) wherein R is as defined for formula (I);
with a solid-phase supported chlorinating agent in the presence of
a base, the kit comprising: (i) a first cartridge containing a
solid-phase supported chlorinating agent; and, (ii) a vial
containing a solution suitable for dissolving the radiolabelled
carboxylic acid of formula (II), or components which can be
reconstituted to form such a solution.
26. A kit as claimed in claim 25, wherein the solid-phase supported
chlorinating agent comprises a chlorinating agent connected by a
linker to a solid support.
27. A kit as claimed in claim 25, wherein the solution for
dissolving the radiolabelled carboxylic acid of formula (II) also
contains a base.
28. A kit as claimed in any one of claims 25 wherein the first
cartridge contains a solid-phase supported base is immobilised on a
solid support.
29. A kit for the radiosynthesis of a radiolabelled product
comprising a kit as claimed in claim 25 and: (iii) a second
cartridge containing a solid-phase supported non-radioactive
precursor of the radiolabelled product.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates to the field of radiosynthetic
chemistry. In particular, the invention relates to a method for the
radiosynthesis of a radiolabelled acid chloride intermediate, which
can be used in the preparation of radiolabelled products such as
radiolabelled amides, amines and esters.
DESCRIPTION OF RELATED ART
[0002] The established radiosynthesis of a radiolabelled acid
chloride intermediate (illustrated as R--COCl below) from CO.sub.2
is via the route:
(i) CO.sub.2+Grignard reagent.fwdarw.R--COOH (ii)
R--COOH+chlorinating agent.fwdarw.R--COCl wherein R can be
aromatic, short or long chain aliphatic. The chlorinating agents
used, such as thionyl chloride and oxalyl chloride, need to be
removed from the reaction mixture once the radiolabelled acid
chloride intermediate has been formed. This is because they are
very reactive and can cause chemical side reactions in any
subsequent reaction in which the radiolabelled acid chloride
intermediate is used. For example, when the subsequent reaction is
between the radiolabelled acid chloride intermediate and an amine,
the reaction between any remaining chlorinating agent and amine
will result in a complex mixture and low yield of radiolabelled
amide product. In addition, chlorinating agents are typically toxic
and as such unsuitable where a compound is being prepared for human
administration. When the radiolabelled acid chloride intermediate
has a relatively low boiling point compared with the chlorinating
agent, separation by distillation may be conveniently carried out
[Luthra et al 1990 Appl. Radiat. Isot., 41(5) pp 471-476]. However,
when the radiolabelled acid chloride intermediate has a relatively
high boiling point compared with the chlorinating agent, separation
by distillation from the chlorinating agent is more difficult and
there is a chance that traces of chlorinating agent will remain in
the final product.
[0003] To resolve the issue of separating radiolabelled acid
chloride intermediates of relatively high boiling point, Luthra et
al [1990 Appl. Radiat. Isot., 41(5) pp 471-476] heated the tubing
between the reaction vessels and succeeded in isolating
[.sup.11C]-cyclobutanecarbonyl chloride (boiling point 140.degree.
C.) from the reaction mixture in a radiochemical yield of between
35 and 60%.
[0004] In another attempt to resolve the separation problems, e.g.,
McCarron et al [1996, J. Label Comp. Radiopharms, 38(10), pp
941-953] used immobilised Grignard reagent in the radiosynthesis of
the relatively involatile acid chloride intermediate,
[carbonyl-.sup.11C]cyclohexanecarbonyl. This meant that only small
quantities of all reagents were required, thereby simplifying the
purification process.
[0005] In addition to problems with removal of chlorinating agents,
any separation step adds time to the radiosynthesis, leading to
decay of the radioisotope, which would be desirably avoided. This
is especially significant where the half-life of the radioisotope
is relatively short, e.g. in the case of .sup.15O (half-life=2.07
minutes), .sup.13N (half-life=9.965 minutes), .sup.11C
(half-life=20.4 minutes) and .sup.18F (half-life=109.7 minutes).
Decay results in a reduction of the specific activity of the
radiolabelled product overtime. Specific activity is particularly
important when the radiolabelled products which are
radiopharmaceuticals, as the non-radioactive cold carrier competes
with the radiolabelled product. Time is therefore a reaction
parameter of equal importance to chemical yield for such
short-lived radiolabelled products. The relationship between time
and concentration of reactants with respect to reaction kinetics is
described in the literature [Langstrom et al, 1981, J. Radionnal.
Chem. 64 pp 273-80].
[0006] A method for the radiosynthesis of radiolabelled acid
chloride intermediates that eliminated the need for a separation
step would therefore be advantageous.
SUMMARY OF THE INVENTION
[0007] The difficulties presented by the prior art methods have
been surmounted by a method which uses a solid phase-supported
chlorinating agent for the conversion of a radioactive carboxylic
acid to a radioactive acid chloride intermediate. As the
chlorinating agent is a solid reagent, there is no chlorinating
agent in the final acid chloride solution. This avoids the
necessity for an additional separation step such that there is no
issue with residual non-radioactive chlorinating agent in the
product. Furthermore, the method can be completed in less time than
the prior art methods.
DETAILED DESCRIPTION OF THE INVENTION
[0008] In a first aspect the present invention relates to a method
for the preparation of a radiolabelled acid chloride compound of
formula (I):
R--COCl (I)
wherein R is C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl,
C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocyclyl,
C.sub.4-C.sub.10 aryl or C.sub.4-C.sub.10 heteroaryl, any of which
may optionally be substituted with NO.sub.2, --O(C.sub.1-C.sub.6
alkyl), C.sub.3-C.sub.10 cycloalkyl or C.sub.4-C.sub.10 aryl; the
method comprising reacting a radiolabelled carboxylic acid of
formula (II):
R--COOH (II)
wherein R is as defined for formula (I); with a solid-phase
supported chlorinating agent in the presence of a base.
[0009] In the context of the present invention, the term
"C.sub.1-C.sub.20 alkyl" refers to a fully saturated straight or
branched hydrocarbon chain containing from 1 to 20 carbon atoms.
Examples include methyl, ethyl, isopropyl, t-butyl and n-decyl. The
term "C.sub.2-C.sub.20 alkenyl" refers to a straight or branched
hydrocarbon chain containing from 2 to 20 carbon atoms and
containing one or more C.dbd.C bonds. Examples include ethenyl,
propenyl and 3-decenyl.
[0010] The term "C.sub.3-C.sub.10 cycloalkyl" refers to a cyclic
fully saturated hydrocarbon group having from 3 to 6 ring carbon
atoms. The cycloalkyl group may comprise either a single ring or a
fused system. Examples include cyclopropyl, and cyclohexyl.
[0011] The term "C.sub.3-C.sub.10 heterocyclyl" refers to a
C.sub.3-C.sub.10 cycloalkyl group as defined above but in which one
of the ring carbon atoms is replaced by --S--, --O-- or --NH--.
Examples include tetrahydrofuranyl, morpholinyl and piperidyl.
[0012] The term "C.sub.4-C.sub.10 aryl" refers to a cyclic
hydrocarbon having aromatic character and containing from 4 to 10
ring atoms. The aryl group may be a single ring, a fused aromatic
system or an aromatic ring fused to a cycloalkyl or heterocyclic
ring. Examples of aryl groups include phenyl, naphthyl and
indolinyl,
[0013] The term "C.sub.4-C.sub.10 heteroaryl" refers to a
C.sub.4-C.sub.10 aryl group as defined above but in which one of
the ring carbon atoms is replaced by --S--, --O-- or --NH--.
Examples include pyridyl, quinolyl and indolyl.
[0014] The term "halo" refers to fluoro, chloro, bromo or iodo.
[0015] Where a compound is defined as "radiolabelled" in the
present invention, this signifies that the compound comprises a
radioactive isotope. The radioactive isotope may be an inherent
part of the compound structure, or may alternatively be chemically
attached to the compound via a suitable chemical group which
optionally comprises a linker.
[0016] In the context of the present invention, a compound which is
"solid-phase supported" is chemically attached to any suitable
solid-phase support which is insoluble in the solvents to be used
in the radiosynthesis.
[0017] Some of the solid phase supported chlorinating agents which
are useful in the present invention comprise a chlorinating agent
connected by a linker to a solid support. Examples of suitable
solid supports include polymers such as polystyrene (which may be
block grafted, for example with polyethylene glycol),
polyacrylamide, or polypropylene or glass or silicon coated with
such a polymer. The solid support may also be in the form of small
discrete particles such as beads or pins, or a coating on the inner
surface of a cartridge or on a microfabricated vessel.
[0018] In this type of structure, the solid-phase supported
chlorinating agent may be, for example, a solid-phase supported
acid chloride, or a solid-phase supported analogue of either
thionyl chloride or oxalyl chloride. The chemical attachment of the
chlorinating agent to the solid support must be such that its
activity as a chlorinating agent is maintained.
[0019] Preferably, the solid-phase supported chlorinating agent is
a solid-phase supported acyl chloride of Formula III:
[solid support-linker--COCl (III)
wherein the linker is a polyethylene glycol linker or comprises up
to four groups selected from: C.sub.4-C.sub.10 aryl or
C.sub.4-C.sub.10 heteroaryl groups; (CH.sub.2).sub.x groups where x
is an integer from 1 to 20; (CH.sub.2).sub.y--O--(CH.sub.2).sub.z
groups where y and z are integers from 1 to 20; or combinations
thereof.
[0020] In the linker groups, any CH.sub.2 group may be replaced by
--O--, --S--, --SO.sub.2-- or --NH.sub.2-- and the linker groups
may be substituted with one or more substituents chosen from OH,
halo, amino, nitro and C.sub.1-C.sub.6 alkoxy.
[0021] A preferred solid-phase supported acyl chloride is of
Formula IIIa:
##STR00001##
[0022] The above solid-phase supported acyl chloride can be
prepared from commercially available polystyrene-supported
carboxylic acid (Novabiochem Cat. No. 01-64-0111), by methods
reported in the literature [Leznoff et al 1977 Can. J. Chem. 55(19)
pp 3351-3355; Meyers et al 1995 Molecular Diversity 1, pp 13-].
These methods describe the transformation of polystyrene-supported
carboxylic acid to polystyrene-supported acyl chloride by treatment
with oxalyl chloride or thionyl chloride (see FIG. 1).
[0023] Alternatively, the solid phase supported chlorinating agent
may be an integral part of a polymer. For example, polymerisation
of a monomer containing an acid anhydride group gives a polymer
which also contains the anhydride group on every unit. Each of the
anhydride groups may then be converted to two acid chloride groups
by known processes, for example by heating the polymer in the
presence of a chlorinating agent such as phosphorus pentachloride
[Hesse et al, 1982, Liebigs Ann. Chem., 11, 2079-2086], thionyl
chloride [Cantrell et al, 1977, J. Org. Chem., 42, 3562-3567] or
zinc chloride [Johnson et al, 1982, J. Am. Chem. Soc., 104,
2190-2198].
[0024] An example of this process for producing solid phase
supported chlorinating agents of this type include the
polymerization of anhydride monomers of type (1) by radical
initiated polymerisation or monomers of type (2) by transition
metal catalysed ring-opening metathesis polymerisation (ROMP)
##STR00002##
followed by their conversion to the equivalent poly(acid
anhydrides).
[0025] In a similar manner an ester-containing monomer can be
polymerised and the ester groups on the polymer converted to acid
chloride groups by reaction with a base such as potassium hydroxide
followed by reaction with a chlorinating agent such as thionyl
chloride [Hagemann et al, 1997, Synth. Commun., 27, 2539-2546]
[0026] An example of this is the radical initiated polymerisation
of monomers of type (3) followed by activation of the ester to the
corresponding solid phase supported acid chloride.
##STR00003##
[0027] The reaction of the compound of formula (II) with the
solid-phase supported chlorinating agent is carried out in the
presence of a base.
[0028] Suitable bases include pyridine derivatives, for example
alkyl pyridines such as di-.sup.tbutylpyridine.
[0029] Alternatively, the base may, like the chlorinating agent, be
immobilised on a solid support. This may be achieved, for example
by polymerization of a pyridine-substituted alkene monomer such as
a vinyl-di-.sup.tbutylpyridine monomer:
##STR00004##
[0030] In another variation, the base may be immobilised in the
same polymer chain as the acid chloride chlorinating agent. This
may be achieved by polymerising a monomer which contains both an
ester or anhydride functional group and a pyridine functional
group. The anhydride or ester groups in the resulting polymer can
be converted to acid chloride functional groups as described above.
An example of this is shown below.
##STR00005##
[0031] Conversion of the radiolabelled carboxylic acid of formula
(II) to the radiolabelled acid chloride compound of formula (I) is
preferably conducted by contacting the solid-phase supported
chlorinating agent with a solution of the carboxylic acid.
[0032] It is greatly preferred to carry out the reaction by passing
the solution of the compound of formula (II) through a column
packed with a resin containing the solid phase supported
chlorinating agent.
[0033] The solution may contain a base or, alternatively, a base
may immobilised on a solid support as described above.
[0034] In a preferred embodiment of the invention, the
radiolabelled acid chloride intermediate is radiolabelled with a
radioactive imaging moiety. The term "radioactive imaging moiety"
in the context of the present invention is taken to mean a
radioactive isotope that may be detected external to the human body
in a non-invasive manner following its administration in vivo.
Examples of suitable radioactive imaging moieties of the present
invention are: [0035] (i) a positron-emitting radioactive non-metal
selected from .sup.11C, .sup.13N, .sup.17F, .sup.18F, .sup.75Br,
.sup.76Br and .sup.124I; or [0036] (ii) a gamma-emitting
radioactive halogen selected from .sup.123I, .sup.125I, .sup.131I
or .sup.77Br.
[0037] A preferred radioactive imaging moiety of the invention is a
positron-emitting radioactive non-metal selected from .sup.11C,
.sup.13N and .sup.18F. These radioactive imaging moieties are
particularly well suited for use as radiopharmaceuticals due to
their physical and biochemical characteristics. In particular, the
relatively short half-lives of these radioactive imaging moieties
means that radiation exposure to a patient undergoing a PET scan is
minimised. It follows that shortening the time taken to produce
radiopharmaceuticals comprising such radioactive imaging moieties
is particularly advantageous.
[0038] When the radioactive imaging moiety of the invention is
.sup.11C, it is preferably an inherent part of the radiolabelled
acid chloride intermediate. Thus, the radiolabelled carboxylic acid
of formula (II) is preferably of the formula R-.sup.11COOH and the
radiolabelled acid chloride compound of formula (I) is preferably
of the formula R-.sup.11COCl.
[0039] .sup.11C may be produced by proton bombardment of natural
nitrogen through the .sup.14N(p,.alpha.).sup.11C nuclear reaction
using a target gas mixture of 2% oxygen in nitrogen to produce
radioactive carbon dioxide (.sup.11CO.sub.2). The .sup.11CO.sub.2
may then be reacted with Grignard reagent to give R-.sup.11COOH and
these steps may also form part of the process of the invention.
[0040] Next, a solution comprising R-.sup.11COOH and any remaining
Grignard reagent is passed through a column containing the
solid-supported acyl chloride of Formula (III). This is illustrated
in FIG. 1, where the acyl chloride is immobilized on a polystyrene
support. An exchange reaction occurs between the excess
solid-supported acyl chloride and the compound of formula (II),
R-.sup.11COON to produce a solution of the compound of formula (I),
R-.sup.11COCl.
[0041] The compound of formula (I) is useful as an intermediate in
the preparation of radiolabelled products.
[0042] Therefore, the method of the invention may include the
additional step of preparing a radiolabelled amide, amine or ester
by reacting a radiolabelled acid chloride compound of formula (I)
as described above with an appropriate reagent.
[0043] The reaction schemes below show reactions of
.sup.11C-labelled acid chlorides of formula (I) but they are also
applicable to reaction schemes below are also illustrative of the
equivalent non-radioactive reactions.
[0044] Radiolabelled amides may be obtained by the following
reaction:
R-.sup.11COCl+R'R''--NH.fwdarw.R-.sup.11CON--R'R''
wherein R is as defined previously; and R' and R'' are each
independently hydrogen, C.sub.1-C.sub.20 alkyl or C.sub.2-C.sub.20
alkenyl, wherein alkyl or alkenyl groups may be substituted with
one or more substitutents chosen from OH, halo, amino, nitro,
C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.10 cycloalkyl,
C.sub.3-C.sub.10 heterocyclyl, C.sub.4-C.sub.10 aryl or
C.sub.4-C.sub.10 heteroaryl, and wherein one or more CH.sub.2
groups of the alkyl or alkenyl chain may be replaced by an --S--,
--O-- or --NH-- group; or R' and R'' may be taken together with the
N to which they are attached to form an aliphatic, aromatic or
partially aromatic N-containing heterocycle having 5 to 30 ring
atoms and up to 6 rings, which may contain one or more additional
heteroatoms selected from N, O and S or in which a ring CH.sub.2
may be replaced by C.dbd.0 and which may be substituted with one or
more substituents selected from C.sub.1-C.sub.20 alkyl,
C.sub.2-C.sub.20 alkenyl, OH, halo, amino, nitro, C.sub.1-C.sub.6
alkoxy, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocyclyl,
C.sub.4-C.sub.10 aryl or C.sub.4-C.sub.10 heteroaryl.
[0045] The corresponding radiolabelled amines can be formed by the
reduction of the radiolabelled amides by lithium aluminum hydride
(LiAlH.sub.4) as follows:
##STR00006##
wherein R, R' and R'' are as defined previously.
[0046] Certain radiolabelled amines can be prepared directly from
the R-.sup.11COCl, for example [.sup.11C]-cyclopentyltheophylline
[Yorke et al 1994 J. Label. Compd. Radiopharm.35 pp 262-3]:
##STR00007##
[0047] Radiolabelled esters may be obtained by the following
reaction:
R-.sup.11COCl+R'''OH.fwdarw.R--CO.sub.2--R'''
wherein R is as defined previously and R''' is a group as defined
previously for R' and R''.
[0048] Preferably, the radiolabelled product is a
radiopharmaceutical, preferred examples [including references to
prior art methods of synthesis] of which are given in Table 1.
TABLE-US-00001 TABLE 1 Structures of preferred radiopharmaceuticals
of the invention Radiopharmaceutical Structure Prior art reference
[carbonyl-.sup.11C]-WAY- 100635 ##STR00008## McCarron et al 1996 J.
Label. Compd. Radiopharm. 38 pp 941-53 [.sup.11C]-propyl-
norapomorphine ##STR00009## Hwang et al 2000 Nucl Med Biol. 27 (6)
pp 533-9 [.sup.11C]-diprenorphine ##STR00010## Luthra et al 1985 J.
Chem. Soc. Comm. 70 pp 1423-5 [.sup.11C]-buprenorphine ##STR00011##
Luthra et al 1987 Appl. Radiat. Isot. 38 pp 65-6 [.sup.11C]-
cyclopentyltheophylline ##STR00012## Yorke et al 1994 J. Label.
Compd. Radiopharm. 35 pp 262-3
[0049] In a further aspect the present invention relates to a kit
for carrying out the method of the invention comprising: [0050] (i)
a first cartridge containing a solid-phase supported chlorinating
agent; and, [0051] (ii) a vial containing a solution suitable for
dissolving the radiolabelled carboxylic acid of formula (II), or
components which can be reconstituted to form such a solution.
[0052] The dissolved radiolabelled carboxylic acid of formula (II)
is passed through the cartridge wherein it reacts with the
solid-phase supported chlorinating agent to form the radiolabelled
acid chloride of formula (I).
[0053] The solution for dissolving the radiolabelled carboxylic
acid of formula (II) may also contain a base, for example a
pyridine base such as di-.sup.tbutoxypyridine. Alternatively, the
first cartridge may contain a solid-phase supported base, which may
be a polymer as defined above.
[0054] Suitable solid-supported chlorinating agents and bases are
as defined above in relation to the first aspect of the
invention.
[0055] In another aspect, the present invention relates to a kit
for the radiosynthesis of a radiolabelled product comprising the
kit for carrying out the method of the invention and: [0056] i) a
second cartridge containing a solid-phase supported non-radioactive
precursor of the radiolabelled product.
[0057] In use, the radiolabelled acid chloride of formula I is
passed through the second cartridge where it reacts with the
solid-phase supported non-radioactive precursor of the
radiolabelled product to form the radiolabelled product.
[0058] Non-radioactive precursors of amines, amides and esters are
described above.
BRIEF DESCRIPTION OF THE EXAMPLES
[0059] Example 1 describes how a polystyrene-supported acyl
chloride is obtained.
[0060] Example 2 describes the radiosynthesis of a [.sup.11C]-acid
chloride.
[0061] Example 3 describes the radiosynthesis of a
[.sup.11C]-amide.
[0062] Example 4 describes the radiosynthesis of a
[.sup.11C]-amine.
BRIEF DESCRIPTION OF THE FIGURES
[0063] FIG. 1 illustrates the reactions involved in the preparation
of the polystyrene-supported acyl chloride and also the
radiosynthesis of the radiolabelled acid chloride intermediate.
EXAMPLES
Example 1
Preparation of Polystyrene-Supported Acyl Chloride
[0064] Polystyrene-supported carboxylic acid [Novabiochem Cat. No.
01-64-0111] is converted to polystyrene-supported acyl chloride by
treatment with either oxalyl chloride or thionyl chloride by
methods disclosed in the prior art [Leznoff et al 1977 Can. J.
Chem. 55 p 3351-, Meyers et al 1995 Molecular Diversity 1 p 13].
FIG. 1 illustrates this reaction.
Example 2
Radiosynthesis of an [.sup.11C]-Acid Chloride
[0065] A solution of [.sup.11C]-labelled carboxylic acid and
Grignard reagent is passed through a column containing
polystyrene-supported acyl chloride. An exchange reaction occurs
between the excess polystyrene-supported acyl chloride and the no
carrier added carboxylic acid to produce a solution of
[.sup.11C]-labelled acid chloride. FIG. 1 illustrates this
reaction.
Example 3
Radiosynthesis of a [.sup.11C]-Amide
[0066] The solution of [.sup.11C]-labelled acid chloride produced
in Example 2 is reacted with a secondary amine to obtain the
respective [.sup.11C]-labelled amide product.
Example 4
Radiosynthesis of a [.sup.11C]-Amine
[0067] The [.sup.11C]-labelled amide product obtained in Example 3
is reduced in the presence of lithium aluminum hydride
(LiAlH.sub.4) to obtain the respective [.sup.11C]-labelled
amine.
Example 5
Radiosynthesis of a [.sup.11C]-Ester
[0068] The [.sup.11C]-labelled acid chloride of Example 2 is
reacted with an alcohol in the presence of pyridine or NaOH to
obtain the respective [.sup.11C]-labelled ester.
* * * * *