Method for halogenating or radiohalogenating a chemical compound

Abstract

A method for obtaining a halogenated organic compound, whereby an organotrifluoroborate compound is reacted with a halide ion in the presence of an oxidizing agent to produce the corresponding halogenated organic compound. The method may be used for producing radiohalogenated organic compounds.

Description

[0001] This application claims the benefit of pending U.S. Provisional Application Ser. No. 60 / 608,186, which was filed on Sep. 9, 2004.

[0002] This invention was developed in part by grants from the U.S. Department of Energy and the National Institutes of Health and the U.S. government may have certain rights in the invention.FIELD OF THE INVENTION

[0003] This invention pertains to the field of labeling a chemical compound, and particularly to the field of attaching a halogen label, such as a radioactive halogen, to an organic chemical compound. BACKGROUND OF THE INVENTION

[0004] Radioisotopes, particularly halogen radioisotopes, have been used extensively in nuclear medicine. The preferred utility of radioiodine in nuclear medicine is based on the availability of relatively reliable techniques of incorporating radiohalogen atoms into organic compounds.

[0005] Many of the presently available radiohalogenation techniques have the common feature that a radionuclide is introduced into ...

Examples

example 1

Production of Organotrifluoroborates

[0035] The procedure for obtaining organotrifluoroborate salts is shown schematically in Scheme 2.

[0036] A solution of a starting organic compound, such as phenylacetylene, (1.02 g, 10.0 mmol) in 20 mL of dry THF was cooled to −78° C. under argon. n-Butyllithium (6.25 mL, 1.60 M in hexane, 10 mmol) was added dropwise and the solution was stirred for one hour. Trimethylborate (1.58 g, 15.0 mmol, 1.5 equiv) was then added dropwise at −78° C. and the solution stirred for one hour. The reaction mixture was then allowed to warm to −20° C. and stirred for an additional hour. A saturated aqueous solution of potassium hydrogen difluoride (4.70 g, 60.0 mmol, 6 equivalents) was added to the vigorously stirred solution. The resulting mixture was allowed to stir for one hour at −20° C., after which it was allowed to warm to room temperature. The solvent was removed under reduced pressure and the resulting white solid was dried under high vacuum for two hou...

example 2

Synthesis of Aryl Iodides

[0038] A variety of aryltrifluoroborates, synthesized as described in Example 1, were subjected to radioiodination using no-carrier added Na123I and peracetic acid in 50% aqueous THF to yield the corresponding aryliodides. The general formula for this reaction is shown below in Scheme 3. All reactions were carried out using dry solvents under an inert atmosphere.

example 2a

Radiosynthesis of 4-[123I]iodoanisole (Representative Procedure)

[0039] Para-methoxyphenyltrifluoroborate (100 μL of 5.2×10−2 solution in 50% aqueous tetrahydrofuran) was placed in a 2 mL Wheaton vial containing no-carrier-added Na123, (37 MBq in 0.1% aqueous NaOH). To this was added peracetic acid (100 μL, 0.3% solution in methanol). The reaction vial was sealed, covered with aluminum foil, and the mixture stirred for 10 min at room temperature. A drop of 10% aqueous sodium thiosulfite was added to decompose excess iodine and the radioiodinated product was isolated by passing it through a silica gel Sep-Pak cartridge using petroleum ether:ethyl acetate (50:1) as eluent. The radiochemical purity of 4-[123I]iodoanisole was determined by radio-TLC (aluminum backed silica gel plate, hexane:ethyl acetate=50:1); Rf=0.55. The TLC retention time (and that of all products) was identical to that of authentic samples. The radiochemical purity was 98% and the radiochemical yield was 88%. The t...

[0001] This application claims the benefit of pending U.S. Provisional Application Ser. No. 60 / 608,186, which was filed on Sep. 9, 2004.

[0002] This invention was developed in part by grants from the U.S. Department of Energy and the National Institutes of Health and the U.S. government may have certain rights in the invention.FIELD OF THE INVENTION

[0003] This invention pertains to the field of labeling a chemical compound, and particularly to the field of attaching a halogen label, such as a radioactive halogen, to an organic chemical compound. BACKGROUND OF THE INVENTION

[0004] Radioisotopes, particularly halogen radioisotopes, have been used extensively in nuclear medicine. The preferred utility of radioiodine in nuclear medicine is based on the availability of relatively reliable techniques of incorporating radiohalogen atoms into organic compounds.

[0005] Many of the presently available radiohalogenation techniques have the common feature that a radionuclide is introduced into ...

Examples

example 1

Production of Organotrifluoroborates

[0035] The procedure for obtaining organotrifluoroborate salts is shown schematically in Scheme 2.

[0036] A solution of a starting organic compound, such as phenylacetylene, (1.02 g, 10.0 mmol) in 20 mL of dry THF was cooled to −78° C. under argon. n-Butyllithium (6.25 mL, 1.60 M in hexane, 10 mmol) was added dropwise and the solution was stirred for one hour. Trimethylborate (1.58 g, 15.0 mmol, 1.5 equiv) was then added dropwise at −78° C. and the solution stirred for one hour. The reaction mixture was then allowed to warm to −20° C. and stirred for an additional hour. A saturated aqueous solution of potassium hydrogen difluoride (4.70 g, 60.0 mmol, 6 equivalents) was added to the vigorously stirred solution. The resulting mixture was allowed to stir for one hour at −20° C., after which it was allowed to warm to room temperature. The solvent was removed under reduced pressure and the resulting white solid was dried under high vacuum for two hou...

example 2

Synthesis of Aryl Iodides

[0038] A variety of aryltrifluoroborates, synthesized as described in Example 1, were subjected to radioiodination using no-carrier added Na123I and peracetic acid in 50% aqueous THF to yield the corresponding aryliodides. The general formula for this reaction is shown below in Scheme 3. All reactions were carried out using dry solvents under an inert atmosphere.

example 2a

Radiosynthesis of 4-[123I]iodoanisole (Representative Procedure)

[0039] Para-methoxyphenyltrifluoroborate (100 μL of 5.2×10−2 solution in 50% aqueous tetrahydrofuran) was placed in a 2 mL Wheaton vial containing no-carrier-added Na123, (37 MBq in 0.1% aqueous NaOH). To this was added peracetic acid (100 μL, 0.3% solution in methanol). The reaction vial was sealed, covered with aluminum foil, and the mixture stirred for 10 min at room temperature. A drop of 10% aqueous sodium thiosulfite was added to decompose excess iodine and the radioiodinated product was isolated by passing it through a silica gel Sep-Pak cartridge using petroleum ether:ethyl acetate (50:1) as eluent. The radiochemical purity of 4-[123I]iodoanisole was determined by radio-TLC (aluminum backed silica gel plate, hexane:ethyl acetate=50:1); Rf=0.55. The TLC retention time (and that of all products) was identical to that of authentic samples. The radiochemical purity was 98% and the radiochemical yield was 88%. The t...

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