JP3134035B2 - Intermediate for synthesis of fluorine radioisotope-labeled compound and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an intermediate for synthesizing a fluorine radioisotope-labeled compound and a method for producing the intermediate.

[0002]

2. Description of the Related Art Positron emission tomography (P) used in positron tomography, which is one of the medical diagnostic imaging techniques
ositron Emission Tomography) (hereinafter referred to as PET)
In the system, fluorine radioisotopes (hereinafter referred to as “ ^18
18 F-L-DOPA labeled with referred to as F "), ¹⁸ F- ¹⁸ F-labeled compound such as dopamine and ¹⁸ F- noradrenaline is used. ¹⁸ FL-Dopa has been used as a diagnostic agent for brain neurotransmission system diseases such as Parkinson's disease and Alzheimer's disease. In addition, dopamine and noradrenaline are substances produced in the metabolic process of L-dopa in vivo, and are known to be neurotransmitters like L-dopa.

As a method for producing an ¹⁸ F-labeled compound, for example, the following methods are known. (1) In US Pat. No. 5,254,726, ¹⁸ O—H ₂ O is irradiated with protons to produce ¹⁸ F− by nuclear conversion,
The solution containing the ¹⁸ F-, and adding an aromatic compound having a nitro group such as nitro veratraldehyde and 6-nitro-pin Pera knurl to a solution in a predetermined solvent, ¹⁸ F-
The aromatic compound is labeled with ¹⁸ F- by a nucleophilic substitution reaction between the compound and a nitro group, and then undergoes necessary reaction and extraction steps to give ¹⁸ FL-dopa, 2- ¹⁸ F-tyrosine, 6 −
¹⁸ F-L-noradrenaline or 6- ¹⁸ F- ¹⁸ F-labeled compound such as dopamine method for synthesizing a (radioactive 2～10MCi) is disclosed. In this way, ¹⁸
In the case of FL-DOPA, p-nitropiperanal is used as a starting material, and (i) a nucleophilic substitution reaction of a nitro group with ¹⁸ F-
It is synthesized through five steps of (ii) reduction reaction, (iii) bromination reaction, (iv) alkylation reaction, and (v) hydrolysis reaction. The various reactions performed here are all liquid reactions.

(2) The Journal of Nuclear Medicine,
Vol. 31 No. 7 July p. 1247-1251 (1990) states that ¹⁸ O-H ₂
O is irradiated with a proton to produce ¹⁸ F- by nuclear transmutation, and this ¹⁸ F- is used in a solution of nitroveratraldehyde or 6-nitropiperanal dissolved in a solvent to give ¹⁸ F- Perform a nucleophilic substitution reaction of the group
After passing through the ¹⁸ F-azlactone compound as a substance on the way, ¹⁸ F
-Method for obtaining L-dopa (synthesis time 100 minutes, radioactivity 5
mCi) are disclosed.

(3) The Journal of Medical Chemistr
y, No. 34, p. 767-771 (1991), ¹⁸ F- was produced by irradiating ¹⁸ O-H ₂ O with protons and performing nuclear conversion.
^{Using 18} F-, a nucleophilic substitution reaction of a nitro group is carried out in a solution in which 3,4-O-isopropylidene-6-nitrobenzaldehyde is dissolved in a solvent. Method for producing ¹⁸ FL-noradrenaline (synthesis time 128 minutes, radioactivity 2-5 mC
i) is disclosed.

[0006]

However, any of the methods of the prior arts (1) to (3) requires a synthesis time of 100%.
In the order long between 130 minutes, during which the ¹⁸ F collapse (half-life: 109.7 min), so that a problem that sufficient yields can not be obtained.

Further, the prior arts (1) to (3) describe a no-carrier-added method (No-Carrier-Adde).
d method: ¹⁸ F produced by irradiating ¹⁸ O—H ₂ O with protons
- Although generates basis by ¹⁸ F compounds in the synthesis method) using a long synthesis time, 3 times extraction process to the extraction of the intermediate product is required, the product to be finally recovered There is a problem that the radioactivity is low. Generally, for ¹⁸ F labeled compounds, at least 3-5 mCi / person of radioactivity is required. For the above reasons, there are many problems in realizing a device, and none of the conventional techniques has been realized.

Further, the method for producing ¹⁸ FL-DOPA of the prior art (1) has a large number of steps of five, which is extremely complicated. Further, nitroveratraldehyde, 6-nitropiperanal and 3,4-O-isopropylidene-6-nitrobenzaldehyde used as raw materials in the prior arts (1) to (3) are all solid at room temperature. The reaction is performed by a liquid-liquid reaction using a solution dissolved in a solvent. For this reason, a step of extracting the product from the mixed solution of the product, unreacted raw materials and impurities after the reaction in each step is required. As a result, the synthesis time becomes longer and the operation is complicated.

[0009] The present invention has been made in view of the above, and provides an ¹⁸ F-labeled compound in a short time and easily.
¹⁸ F ¹⁸ F-labeled compound synthesis intermediates for the synthesis of labeled compounds and a manufacturing method thereof.

[0010]

The present invention provides a compound represented by the general formula (I):
Provided is an intermediate for synthesizing an ¹⁸ F-labeled compound shown in (1).

[0011]

Embedded image (Where

[0012]

Embedded image The present invention also provides a method for producing an intermediate for synthesizing an ¹⁸ F-labeled compound represented by the general formula (I),

[0013]

Embedded image (Where

[0014]

Embedded image (A) nitrating a compound represented by the general formula (II)
Obtaining a compound represented by (III), and

[0015]

Embedded image

(B) Compound (III) obtained in step (a)
Characterized by comprising a step of condensing via an ether bond to a cross-linked chloromethylstyrene-styrene copolymer carrier obtained by cross-linking with a divinylbenzene to obtain an intermediate (I) for synthesizing an ¹⁸ F-labeled compound, Provided is a method for producing an intermediate for compound synthesis.

Hereinafter, the present invention will be described in more detail. The intermediate (I) for synthesizing an ¹⁸ F-labeled compound of the present invention is a cross-linked chloromethylstyrene cross-linked with divinylbenzene.
Styrene copolymer carrier (hereinafter simply referred to as "carrier")
In addition, a 2-methoxy-4-nitro-5-formylphenyl group as a reaction substrate is condensed through an ether bond.

The carrier used in the present invention is a crosslinked chloromethylstyrene-styrene copolymer crosslinked with divinylbenzene, and the molar ratio of the chloromethylstyrene monomer to the styrene monomer is, for example, from 1: 100 to 1: 100.
One. This polymer is crosslinked with divinylbenzene to form a three-dimensional structure. Divinylbenzene is, for example, 1 to 10% by weight based on the whole copolymer.

The intermediate for synthesizing the ¹⁸ F-labeled compound of the present invention is
The reactive substrate described above is bonded to the reactive group chloromethyl group of the chloromethylstyrene monomer on the main chain of the above-mentioned crosslinked chloromethylstyrene-styrene copolymer by an ether bond.

The above-mentioned ¹⁸ F-labeled compound of the present invention can be produced, for example, as follows. Step (a) Isovanillin (3) of compound (II) which is one of the starting materials
-Hydroxy-4-methoxybenzaldehyde) is commercially available.

The compound (II) is nitrated to introduce a nitro group at the 6-position. The nitration of the compound (II) can be carried out by a usual nitration reaction, for example, as follows. First, fuming nitric acid is added dropwise while maintaining a solution of compound (II) in acetone at 10 ° C. or lower. The reaction solution is dropped into ice water, and the generated precipitate is collected by filtration. Dissolve the precipitate in sodium hydroxide solution. Carbon dioxide gas is passed through the obtained solution, and the generated precipitate is collected. The precipitate is recrystallized from ethanol to give compound (III).

Step (b) Next, the compound (III) obtained in the step (a) is condensed via an ether bond to a crosslinked chloromethylstyrene-styrene copolymer carrier crosslinked with divinylbenzene to form an intermediate (I) Get.

The binding of the reaction compound (III) to the carrier is carried out, for example, as follows. First, compound (III) is mixed with an alkali metal hydroxide MOH (eg, potassium hydroxide, sodium hydroxide) in a polar solvent,
For example, heating is performed at 50 to 150 ° C. for 5 to 24 hours. Here, as the polar solvent, for example, alcohols such as methanol, ethanol, propanol, and butanol, dimethyl sulfoxide, and dimethylformamide can be used. As a result, a compound represented by the general formula (IV) is obtained.

[0024]

Embedded image

After completion of the reaction, the above-mentioned carrier is added to the reaction solution, and the mixture is heated and reacted at, for example, 50 to 150 ° C. for 5 to 24 hours to obtain the compound (IV) and the chloromethyl group of the chloromethylstyrene monomer of the carrier. And an ether bond is formed to form ¹⁸ F represented by the above general formula (I).
An intermediate for labeling compound synthesis is obtained. ^{Using the} intermediate (I) for synthesizing an ¹⁸ F-labeled compound, for example, ¹⁸ FL-DOPA can be produced as shown in the reaction formula (1).

[0026]

Embedded image

First, the nitro group of the intermediate (I) is subjected to nucleophilic substitution with ¹⁸ F to obtain an intermediate (V). ¹⁸ F nucleophilic substitution reaction, for example, ¹⁸ F-labeled compound synthesis intermediates a column packed with (I), filled with a solution prepared by dissolving in dimethyl sulfoxide [K _222] + · ¹⁸ F- salt, 120-140 ℃,
This is done by heating for 15-20 minutes. here,
K ₂₂₂ indicates a cryptand: C ₁₈ H ₃₆ N ₂ O ₈ .

As a result, the generated ¹⁸ F nucleophilic substitution compound site (for example, 2-methoxy-4- ¹⁸ fluoro-5-formyl-phenyl group) is bonded to the carrier by an ether bond, and thus, for example, acetonitrile or the like is used. The unreacted material can be easily separated by washing the inside of the column with the above solvent. Further, the solvent can be removed by heating the column.

[0029] ¹⁸ F- can be produced by a usual nuclear conversion technique. For example, it can be produced by irradiating ¹⁸ O—H ₂ O with protons in a cyclotron to perform nuclear conversion.

Next, the obtained intermediate (V) and 2-phenyl-5-oxazolone are subjected to aldol condensation in the presence of a base to obtain an azlactone derivative represented by the general formula (VI). Here, as the base, for example, 1,4-diazabicyclo [2,2,2] octane can be used. More specifically, for example, 1,4-diazabicyclo [2,2,
2] An alcohol solution in which octane is dissolved is mixed with the compound (I
V) and packed at 130-150 ° C.
Heat for ~ 15 minutes. The alcohol used here is
For example, methanol, ethanol, propanol, 2-
Propanol, butanol or 2-butanol.

The generated ¹⁸ F azlactone compound site is
Since it is bonded to the carrier, the inside of the column can be washed with a solvent such as methanol and easily separated from unreacted substances. The solvent can be removed by heating and evaporating the column.

Next, the azlactone derivative (VI) is subjected to a reduction reaction. As a result, the benzyl ether bond between the ¹⁸ F azlactone compound site and the carrier is reductively cleaved, and the methoxy group at the 2-position also has a methyl group-
The ether bond between the phenyl groups is reductively cleaved.
Also, the CN and CO bonds of the 5-membered ring of azlactone are cleaved. As a result, the ¹⁸ F-
A D, L-dopracemic mixture is obtained.

In the reduction reaction of compound (VI), for example, a hydroiodic acid solution stabilized with hypophosphorous acid is filled in a column filled with azlactone derivative (VII),
It can be performed by heating at 0 ° C. for 10 to 20 minutes. Thereafter, for example, H ₂ O can be passed through the column and the product can be eluted from the support. Then, the eluate can be neutralized with, for example, sodium hydroxide to recover the ¹⁸ FD, L-dopaseracemic mixture (VII).

In the above-mentioned reduction reaction, red phosphorus can be used as a catalyst. Further, a solution obtained by dissolving hydroxylamine hydrochloride in glacial acetic acid and ethanol and then diluting with water can be added to a hydroiodic acid solution stabilized with hypophosphorous acid.

[0035] Finally, ¹⁸ F-D, L- Doparasemi mixture (VII), according to a conventional method, ¹⁸ F purposes and racemic separation
-To obtain L-dopa. Racemic separation can be performed, for example, using ¹⁸ F-
The D, L-dope parasemi mixture (VII) can be extracted by HPLC (high performance liquid chromatography).

In the production of the above-mentioned ¹⁸ F-labeled compound, the intermediate for synthesizing the ¹⁸ F-labeled compound represented by the general formula (I) comprises a 2-methoxy-4-nitro-5-formyl-phenyl group as a reaction substrate. It is ether-bonded to the crosslinked chloromethylstyrene-styrene copolymer carrier. Therefore, the reaction between the reaction substrate and the reaction reagent is performed by a solid-liquid reaction. Therefore,
By washing the reaction product-carrier complex with an appropriate solvent, unreacted reaction reagents and impurities can be easily removed. As a result, it is possible to perform the isolation of the desired product which is required for each step very easily, ¹⁸
It is possible to simplify the operation necessary for the production of the F-labeled compound and to significantly reduce the required time. In particular, in the manufacturing method according to a conventional liquid-liquid reaction, the reaction product was subjected to extraction using an extraction jig for each step it was necessary to isolate, ¹⁸ F-labeled compound synthesis of the present invention In the case where the intermediate for use is used, the extraction operation only needs to be performed during the final racemic separation. Therefore, the use of the intermediate for synthesizing the ¹⁸ F-labeled compound of the present invention can be carried out with an inexpensive production apparatus and is economically useful. Also, there is an advantage that it is not necessary to use a reagent such as a lithium catalyst which is difficult to handle.

In the conventional method, 5 mC is required for synthesis once a day.
Only i can be collected. In addition, this recovery amount is an amount obtained when the synthesis is successful, and in many cases, the synthesis actually fails at the medical site and a desired recovery amount cannot be obtained. For this reason, the required amount is often not obtained once every two or three times. However, if the intermediate for synthesizing the ¹⁸ F-labeled compound of the present invention is used, the recovered amount is large and the recovered amount does not become insufficient, and the required amount of ¹⁸ FL-DOPA is reliably produced at the medical site each time. can do.

The crosslinked chloromethylstyrene-styrene copolymer carrier is chemically stable, has high physical strength, and has high thermal stability. Therefore, it is stable even when exposed to high-temperature conditions of 120 to 260 ° C. in the ¹⁸ F nucleophilic substitution reaction, the synthesis of an azlactone derivative by aldol condensation, and the reduction reaction.

[0039]

Embodiments of the present invention will be described below in detail. Example 1 10 g of isovanillin (manufactured by Aldrich) was added to acetone 5
While maintaining the solution dissolved in 0 ml at 4 ° C. or lower, fuming nitric acid was added dropwise. The reaction solution was dropped into 2000 ml of ice water,
The precipitate formed was collected by filtration. 0.5 precipitate
It was dissolved in an N-sodium hydroxide solution (350 ml), carbon dioxide gas was passed through the solution, and the resulting precipitate was collected by filtration. The precipitate was once dissolved in ethanol (200 ml), and crystals precipitated by recrystallization were recovered.

The obtained recrystallized product (1.0 g) and potassium hydroxide (0.4 g) were dissolved in methanol (100 ml), and the mixture was heated at a reflux temperature of methanol of 64 ° C. (1 atm) and reacted for 7 hours. Was. After completion of the reaction, a crosslinked chloromethylstyrene having a three-dimensional structure in which 2% by weight of divinylbenzene was randomly crosslinked with respect to the total weight was added to the reaction solution.
Styrene copolymer (molar ratio 1: 9) (Wako Pure Chemical Industries, Ltd.)
Was added, and heated at 64 ° C. to react for 24 hours. As a result, 2-methoxy-5-formyl-4-nitrophenoxymethylstyrene-styrene copolymer ( ¹⁸
5.8 g of an intermediate for synthesizing an F-labeled compound) was obtained.

The physical data of the obtained intermediate for synthesizing the ¹⁸ F-labeled compound were as follows. IR ν (cm ⁻¹ ) 3101.01 3081.73 3058.59
3025.80 3000.73 2921.66 2848.38 1941.99 1868.71 1801.21
1718.28 1600.65 1583.29 1540.86 1492.65 1452.15 1371.16
1326.80 1313.30 1267.02 1180.24 1155.17 1068.38 1027.89
979.67 966.17 941.10 906.39 840.82 796.47 755.97 698.11 61
9.05 539.98 3079.80 Aromatic CH stretching vibration 3058.59 3025.80 2921.66 Methylene CH stretching vibration 2850.31 1943.92 Overtone vibration or coupled vibration absorption band 1872.56 1803.74 1720.21 1700.93 1600.65 In-plane skeletal vibration due to aromatic ring stretching 1542.79 1490.72 1448.30 1400-800 fingerprint Aromatic C—H out-of-plane bending vibration 698.11 (Polystyrene excess due to monosubstituted benzene ring pattern) 800 to 700 (s) C—Cl stretching vibration • —CH ₂ —O—Φ— and RO—Φ— ( Characteristic absorption derived from ether bond) C—OC Inverse symmetric stretching vibration around 1250 (s) C—O—C Symmetric stretching vibration around 1050 (s) Characteristic absorption derived from —NO ₂ (nitro group) O = N = O Anti-symmetric stretching vibration 1550-1500 (s) O = N = O Symmetric stretching vibration 1360-1290 (s) CN stretching vibration Around 870 (s) ・ Characteristic absorption derived from -CHO (aldehyde group) Aldehyde CH Stretching vibration 2900-2700 (w) aldehyde -H deformation vibration 1390 near (s) C = O stretching vibration 1700 near (s) Elemental analysis:

[0042]

[Table 1]

Example 2 Fuming nitric acid was added dropwise while keeping a solution of 10 g of isovanillin in 50 ml of acetone at 4 ° C. or less. The reaction solution was dropped into 2000 ml of ice water, and the formed precipitate was collected by filtration. The precipitate was dissolved in a 0.5N sodium hydroxide solution (350 ml), carbon dioxide gas was passed through the solution, and the formed precipitate was collected by filtration. The precipitate was once dissolved in ethanol (200 ml), and crystals precipitated by recrystallization were recovered.

The obtained recrystallized product (1.0 g) and potassium hydroxide (0.4 g) were mixed with methyl sulfoxide (100 m
l) and dissolved in dimethyl sulfoxide at a reflux temperature of 100.
The reaction was performed by heating at 1 ° C. (1 atm) for 10 hours. After completion of the reaction, 5 g of a crosslinked chloromethylstyrene-styrene copolymer (molar ratio 1: 9) as in Example 1 was added to the reaction solution, and the mixture was heated at 100 ° C. and reacted for 24 hours. As a result, 5.8 g of a 2-methoxy-5-formyl-4-nitrophenoxymethylstyrene-styrene copolymer (intermediate for synthesizing an ¹⁸ F-labeled compound) was obtained.

The physical data of the obtained intermediate for synthesizing the ¹⁸ F-labeled compound were the same as those in Example 1. Example 3 Fuming nitric acid was added dropwise while keeping a solution of 10 g of isovanillin in 50 ml of acetone at 4 ° C. or lower. The reaction solution was dropped into 2000 ml of ice water, and the formed precipitate was collected by filtration. The precipitate was dissolved in a 0.5N sodium hydroxide solution (350 ml), carbon dioxide gas was passed through the solution, and the formed precipitate was collected by filtration. The precipitate was once dissolved in ethanol (200 ml), and crystals precipitated by recrystallization were recovered.

The obtained recrystallized product (1.0 g) and potassium hydroxide (0.4 g) were dissolved in ethanol (100 ml) and reacted at a reflux temperature of ethanol of 78 ° C. (1 atm) for 10 hours. Was. After completion of the reaction, 5 g of a crosslinked chloromethylstyrene-styrene copolymer (molar ratio 1: 9) as in Example 1 was added to the reaction solution, and the mixture was heated at 78 ° C. and reacted for 24 hours. As a result, 2-methoxy-5
-Formyl-4-nitrophenoxymethylstyrene-styrene copolymer (intermediate for synthesizing an ¹⁸ F-labeled compound) 5.8
g was obtained.

The physical data of the obtained intermediate for synthesizing the ¹⁸ F-labeled compound were the same as those in Example 1. Next, the case where ¹⁸ FL-DOPA was synthesized using the intermediate for synthesizing ¹⁸ F-labeled compound obtained in Example 1 will be described.

First, the product [K
₂₂₂ ] + ¹⁸ F- (29 mg) / dimethyl sulfoxide solution (1 ml) was immersed in ¹⁸ g of the intermediate A for synthesizing the ¹⁸ F-labeled compound obtained in Example 1 and heated at 140 ° C. for 15 minutes to give ¹⁸ F- A nucleophilic substitution reaction of the nitro group was carried out. After heating, it was washed with acetonitrile (15 ml) to remove impurities. As a result, ^{2-methoxy-4-18-fluoro} -
A 5-formyl-phenoxymethylstyrene-styrene copolymer (intermediate B) was obtained.

Next, 2-phenyl-5-oxazolone (50 mg) and 1,4-diazabicyclo [2,2,
2] Intermediate B was immersed in a solution of octane (100 mg) dissolved in ethanol (1 ml), heated at 140 ° C. for 10 minutes, and an azlactone introduction reaction was performed by aldol condensation. After the completion of the reaction, impurities were removed by washing with ethanol (15 ml). As a result, 2-methoxy- ^4-18
A fluoro-5- (5-oxo-2-phenyl-4-oxazolinylidenemethyl) phenoxymethylstyrene-styrene copolymer (intermediate C) was obtained.

Further, the intermediate (C) which had been subjected to an azlactone introduction reaction was immersed in hydroiodic acid stabilized with hypophosphorous acid (50 μl) and containing red phosphorus (100 mg).
Heated at 0 ° C. for 15 minutes under a nitrogen atmosphere.

The solution containing the product was neutralized with 6N-sodium hydroxide, and after removing red phosphorus by filtration, a 0.1% acetic acid aqueous solution was added to the filtrate. This aqueous solution is added to Whatman Pa
rtisil 10 ODS-3 reverse phase column (trade name:
(Manufactured by Whatman Co., Ltd.) at a flow rate of 4 ml / min, and components eluted after 17 minutes were collected. The resulting component was an ¹⁸ FD, L-dopaseracemic mixture. FIG. 1 shows the results of the liquid chromatography. ¹⁸ F-
The elution time of the D, L-dope parasemi mixture was determined by The Journa
l of Nuclear Medicine vol. 31, No.7, July 1990 P.1
It was consistent with the data shown in 247-1251.

Next, in order to carry out the racemic resolution, the eluate containing the ¹⁸ FD, L-dopracemic mixture obtained in the previous step was washed with sodium dihydrogen phosphate (5 × 10 −2 M) and CuSO 4 ( 10-3M) immersed in an aqueous solution,
Cu = Si 100 column (trade name: Polylab-
(Serva product) at a flow rate of 1.5 ml / min. At this time, ¹⁸ FL-dopa was eluted after 9 minutes, the synthesis time until obtaining the final product ( ¹⁸ FL-dopa) was 80 minutes, and the radioactivity was 25 mCi.

[0053]

According to the intermediate for synthesizing an ¹⁸ F-labeled compound of the present invention, a reaction substrate is condensed to a crosslinked chloromethylstyrene-styrene copolymer by an ether bond. For this reason
¹⁸ using F-labeled compound synthesis intermediates, in the case of performing the synthesis of ¹⁸ F-labeled compound, reaction between the reaction substrate and reagent is carried out by solid-liquid reaction. Therefore, by washing the reaction product-carrier complex with an appropriate solvent, an unreacted product can be easily isolated from the reaction product (solid). As a result, the extraction operation of the reaction product in the production by the conventional liquid-liquid reaction can be performed only by the washing operation with the solvent,
The manufacturing process can be simplified and the manufacturing time can be significantly reduced. Further, the reaction products - since carrier complex can all be provided in the next reaction, the final ¹⁸ F-L-dopa yield is improved, and a sufficient yield ¹⁸ F-L-dopa Can be synthesized from ¹⁸ F-. As a result, ¹⁸ FL-DOPA having high specific activity can be easily produced.

[Brief description of the drawings]

FIG. 1 is a characteristic diagram showing results of liquid chromatography of ¹⁸ F-dopa in an example of the present invention.

────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Shigeki Yamazaki 1-1-2 Marunouchi, Chiyoda-ku, Tokyo Nippon Kokan Co., Ltd. (72) Inventor Katsuhiko Osaki 1-1-2 Marunouchi, Chiyoda-ku, Tokyo Nippon Kokan Inside (72) Inventor Kenichiro Mizuno 1-2-1, Marunouchi, Chiyoda-ku, Tokyo Inside Nippon Kokan Co., Ltd. (72) Inventor Masao Kato 460-167 Kamihirooka, Tsukuba City, Ibaraki Prefecture (72) Inventor Kazunori Kataoka Chiba 1083-4, Omuro, Kashiwa City, Prefecture (56) References JP-A-2-110107 (JP, A) JP-A-61-205931 (JP, A) JP-A-5-230149 (JP, A) JP-A Sho53 -28690 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C08F 12/12 C08F 8/00-8/50

Claims (2)

(57) [Claims] 1. An intermediate for synthesizing a fluorine radioisotope-labeled compound represented by the general formula (I). Embedded image (Wherein, 2. A method for producing an intermediate for synthesizing a fluorine radioisotope-labeled compound represented by the general formula (I), comprising: (Wherein, (A) nitrating a compound represented by the general formula (II)
A step of obtaining a compound represented by (III), and (B) The compound (III) obtained in the step (a) is condensed by an ether bond to a cross-linked chloromethylstyrene-styrene copolymer carrier cross-linked with divinylbenzene to form an intermediate (I) for synthesizing a fluorine radioisotope-labeled compound. A method for producing an intermediate for synthesizing a fluorine radioisotope-labeled compound, the method comprising: