WO2011078296A1 - 2-クロロ-3-トリフルオロメチルピリジンの製造方法 - Google Patents
2-クロロ-3-トリフルオロメチルピリジンの製造方法 Download PDFInfo
- Publication number
- WO2011078296A1 WO2011078296A1 PCT/JP2010/073252 JP2010073252W WO2011078296A1 WO 2011078296 A1 WO2011078296 A1 WO 2011078296A1 JP 2010073252 W JP2010073252 W JP 2010073252W WO 2011078296 A1 WO2011078296 A1 WO 2011078296A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- trifluoromethylpyridine
- chloro
- oxide
- chlorinating agent
- solution
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
Definitions
- the present invention relates to a method for producing 2-chloro-3-trifluoromethylpyridine useful as an intermediate for pharmaceuticals and agricultural chemicals.
- Patent Document 1 and Patent Document 2 describe methods for producing 2-chloro-3-trifluoromethylpyridine by reacting 3-trifluoromethylpyridine and chlorine, respectively. -It was not always satisfactory in terms of the production rate of trifluoromethylpyridine.
- Non-Patent Document 1 describes a method for producing ethyl 2-chloro-3-pyridinecarboxylate by reacting 3-ethoxycarbonylpyridine N-oxide with phosphorus oxychloride. -No description is given of a method for producing trifluoromethylpyridine.
- the present invention relates to a method for producing 2-chloro-3-trifluoromethylpyridine or a salt thereof, characterized by reacting 3-trifluoromethylpyridine N-oxide with a chlorinating agent, 2-chloromethyl characterized by oxidizing 3-fluoromethylpyridine N-oxide by oxidizing fluoromethylpyridine and then reacting the resulting 3-trifluoromethylpyridine N-oxide with a chlorinating agent
- the present invention relates to a method for producing -3-trifluoromethylpyridine or a salt thereof.
- 2-chloro-3-trifluoromethylpyridine can be produced with a high production rate and a high yield.
- 2-Chloro-3-trifluoromethylpyridine can be produced by reacting 3-trifluoromethylpyridine N-oxide with a chlorinating agent.
- a salt of 2-chloro-3-trifluoromethylpyridine can be produced according to a usual salt formation reaction, and examples of the salt include acid addition salts such as hydrochloride and sulfate.
- chlorinating agents include acid chlorides such as acetyl chloride, trichloroacetyl chloride, and benzoyl chloride; sulfonic acid chlorides such as methanesulfonyl chloride and benzenesulfonyl chloride; quaternary ammonium such as tetraethylammonium chloride and tetrabutylammonium chloride. Salt; phosgene, diphosgene, triphosgene, oxalyl chloride, phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, sulfuryl chloride, hydrogen chloride and the like.
- acid chlorides such as acetyl chloride, trichloroacetyl chloride, and benzoyl chloride
- sulfonic acid chlorides such as methanesulfonyl chloride and benzenesulfonyl chloride
- oxalyl chloride and phosphorus oxychloride are preferable, and oxalyl chloride is more preferable.
- oxalyl chloride is used as a chlorinating agent, the production rate and yield of 2-chloro-3-trifluoromethylpyridine are remarkably improved.
- the chlorinating agent is preferably used in an amount of usually 1 to 10 times mol, more preferably 1 to 3 times mol per mol of 3-trifluoromethylpyridine N-oxide. However, depending on the reaction conditions, an amount outside this range can be used.
- This reaction can usually be performed in the presence of a solvent.
- the solvent is not particularly limited as long as it is inert to the reaction.
- the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane and cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated compounds such as chlorobenzene, dichlorobenzene, dichloromethane and dichloroethane.
- ethers such as diethyl ether, butyl ethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, dimethoxyethane; acetonitrile, propionitrile, N, N-dimethylformamide, dimethyl sulfoxide, sulfolane, N, N- Polar aprotic solvents such as dimethylacetamide, N-methylpyrrolidone; esters such as methyl acetate, ethyl acetate, propyl acetate; acetone, methyl ethyl ketone, methyl isobutyl ketone Or the like can be mentioned ketones such as.
- halogenated hydrocarbons are preferable, and dichloromethane and dichloroethane are more preferable.
- dichloromethane or dichloroethane is used as a solvent, the production rate and yield of 2-chloro-3-trifluoromethylpyridine are remarkably improved.
- This reaction can be performed in the presence of a base, if necessary.
- the base include alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; alkali metal acetates such as sodium acetate and potassium acetate; trimethylamine and triethylamine , Diisopropylamine, triisopropylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, 2,6-dimethylpyridine, 4-pyrrolidinopyridine, N-methylmorpholine, N, N-dimethylaniline, N, N-diethylaniline Tertiary amines such as N-ethyl-N-methylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene, 1,4-diazabicyclo [2.2.2] octane, etc.
- tertiary amines are preferable, and triethylamine is more preferable.
- triethylamine is used as a base, the production rate and yield of 2-chloro-3-trifluoromethylpyridine are remarkably improved.
- the base is preferably used in an amount of usually 1 to 10 times mol, more preferably 1 to 3 times mol, per mol of 3-trifluoromethylpyridine N-oxide. However, depending on the reaction conditions, an amount outside this range can be used.
- a base and a chlorinating agent can be added in arbitrary orders.
- the base may be added before or after the chlorinating agent is added, or may be added simultaneously with the chlorinating agent. Particularly when a base is used, the production rate and yield of 2-chloro-3-trifluoromethylpyridine are remarkably improved by adding the base after adding the chlorinating agent.
- the reaction temperature is usually preferably about ⁇ 60 to 150 ° C., more preferably about ⁇ 40 to 130 ° C.
- the reaction time is usually preferably about 0.1 to 24 hours, more preferably about 0.5 to 12 hours.
- the reaction temperature is usually preferably about ⁇ 40 to 20 ° C., more preferably about ⁇ 30 to 10 ° C.
- the production rate and yield of 2-chloro-3-trifluoromethylpyridine are remarkable when the reaction temperature is preferably ⁇ 40 to 20 ° C., more preferably ⁇ 30 to 10 ° C. To improve.
- 2-Chloro-3-trifluoromethylpyridine oxidizes 3-trifluoromethylpyridine to produce 3-trifluoromethylpyridine N-oxide, and then the resulting 3-trifluoromethylpyridine N-oxide and chlorine It can be produced by reacting with an agent. In this case, 3-trifluoromethylpyridine N-oxide can be reacted with a chlorinating agent without isolation or purification.
- Oxidation is performed by reacting 3-trifluoromethylpyridine with an oxidizing agent.
- the oxidizing agent include peracids such as peracetic acid, perbenzoic acid, and m-chloroperbenzoic acid; hydroperoxides such as cumyl hydroperoxide and tert-amyl hydroperoxide; and hydrogen peroxide.
- peracetic acid, tert-amyl hydroperoxide, hydrogen peroxide and the like are preferable.
- the oxidizing agent is preferably used in an amount of usually 1 to 10 times mol, more preferably 1 to 3 times mol for 1 mol of 3-trifluoromethylpyridine. However, depending on the reaction conditions, an amount outside this range can be used.
- This reaction can usually be performed in the presence of a solvent.
- the solvent is not particularly limited as long as it is inert to the reaction.
- the solvent include aliphatic hydrocarbons such as pentane, hexane, heptane, octane and cyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated compounds such as chlorobenzene, dichlorobenzene, dichloromethane and dichloroethane. Examples thereof include hydrocarbons; organic acids such as acetic acid and propionic acid; water and the like.
- the reaction temperature is usually preferably about 0 to 150 ° C, more preferably about 10 to 120 ° C.
- the reaction time is usually preferably about 0.1 to 24 hours, more preferably about 0.5 to 12 hours.
- Example 1 A four-necked flask equipped with a stirrer, a thermometer, and a condenser tube was charged with 147.0 g of 3-trifluoromethylpyridine and 367.75 g of acetic acid. Thereto, 141.71 g of 30% hydrogen peroxide solution was added at 20 to 30 ° C. and reacted at 80 to 90 ° C. for 7 hours. After cooling the reaction solution, 31.51 g of sodium sulfite was added at 30 ° C. or lower. After the addition, the mixture was stirred at 30 to 40 ° C.
- reaction solution was heated under reduced pressure (15 mmHg) until the internal temperature reached 50 ° C., and acetic acid was distilled off. 441 mL of water was added thereto, and 204.26 g of 30% aqueous sodium hydroxide solution was added dropwise at 20 ° C. or lower to adjust the pH to 8.0.
- the reaction solution was analyzed by liquid chromatography. 0.35% of 3-trifluoromethylpyridine N-oxide, 91.89% of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethyl It was confirmed that pyridine was contained at a ratio of 0.72%.
- the reaction solution was poured into 24.45 g of ice water at 10 ° C. or lower, stirred at 10 to 20 ° C. for 30 minutes, and then separated. The obtained organic layer was washed with water to obtain 43.1 g of a 1,2-dichloroethane solution containing 2-chloro-3-trifluoromethylpyridine.
- the obtained solution was analyzed by liquid chromatography, and it was confirmed that the solution contained 4.25 g of 2-chloro-3-trifluoromethylpyridine.
- Example 2 A four-necked flask equipped with a stirrer, thermometer and drying tube was charged with 32.62 g of 3-trifluoromethylpyridine N-oxide and 46.0 g of phosphorus oxychloride and reacted at 105 to 110 ° C. for 2 hours, Further reaction was carried out at 120 to 125 ° C. for 5 hours. The reaction solution was analyzed by liquid chromatography, 0.16% of 3-trifluoromethylpyridine N-oxide, 50.34% of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethyl. It was confirmed that pyridine was contained in a proportion of 25.34%.
- the reaction solution was heated under reduced pressure (100 mmHg) until the internal temperature reached 75 ° C., and excess phosphorus oxychloride was distilled off.
- the reaction solution was added to 163.1 g of ice water and stirred at 30 ° C. or lower for 1 hour. Thereafter, the mixture was extracted with 1,2-dichloroethane, stirred for 30 minutes and separated. The obtained organic layer was washed with water to obtain 132.11 g of a 1,2-dichloroethane solution containing 2-chloro-3-trifluoromethylpyridine.
- the obtained solution was analyzed by liquid chromatography, and it was confirmed that 13.17 g of 2-chloro-3-trifluoromethylpyridine was contained in the solution.
- Example 3 A four-necked flask equipped with a stirrer, a thermometer, and a condenser tube was charged with 238.63 g of 3-trifluoromethylpyridine and 596.57 g of acetic acid. Thereto, 229.85 g of 30% hydrogen peroxide water was added at 20 to 30 ° C. and reacted at 80 to 90 ° C. for 7 hours. After cooling the reaction solution, 51.11 g of sodium sulfite was added at 30 ° C. or lower. After the addition, the mixture was stirred at 30 to 40 ° C. for 3 hours, and it was confirmed by potassium iodide starch paper that the treatment of excess hydrogen peroxide in the reaction solution was completed.
- the reaction solution was heated under reduced pressure (15 mmHg) until the internal temperature reached 55 ° C., and acetic acid was distilled off. 357.9 mL of water was added thereto, and 343.2 g of 30% aqueous sodium hydroxide solution was added dropwise at 15 ° C. or lower to adjust the pH to 8.0. Thereafter, the warm extraction with 633.1 g of dichloromethane was repeated twice at 30 to 40 ° C. Next, the dichloromethane extraction solution was heated under normal pressure until the internal temperature reached 50 ° C. to distill off the dichloromethane, and the water in the system was removed to remove 3-trifluoromethylpyridine N-oxide (melting point: 76.0 ° C. ) 811.9 g of dichloromethane solution containing 259.57 g was obtained.
- reaction solution was analyzed by liquid chromatography. 0.24% of 3-trifluoromethylpyridine N-oxide, 90.93% of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethyl It was confirmed that pyridine was contained at a ratio of 0.52%.
- the reaction solution was poured into 1019.3 g of ice water at 10 ° C. or lower, stirred at 10-20 ° C. for 1 hour, and then separated. To the obtained organic layer, 407.8 g of water was added, and 26.7 g of 30% aqueous sodium hydroxide solution was added dropwise at 20-30 ° C.
- Example 4 In a four-necked flask equipped with a stirrer, thermometer, drying tube and dropping funnel, 23.65 g of a 1,2-dichloroethane solution containing 3.26 g of 3-trifluoromethylpyridine N-oxide (13.78% solution) Was charged. Thereto, 3.05 g of oxalyl chloride was added dropwise at 0 to 5 ° C. and reacted at the same temperature for 1 hour. To the reaction solution, a mixed solution of 2.42 g of triethylamine and 4.08 g of 1,2-dichloroethane was added dropwise at 0 to 10 ° C. over 1 hour, and the mixture was further reacted at the same temperature for 2 hours.
- reaction solution was analyzed by liquid chromatography. 39.72% of 3-trifluoromethylpyridine N-oxide, 54.63% of 2-chloro-3-trifluoromethylpyridine, 2-chloro-5-trifluoromethyl It was confirmed that pyridine was contained at a ratio of 1.31%.
- Example 5 A four-necked flask equipped with a stirrer, thermometer, drying tube and dropping funnel was charged with 124.49 g (13.10% solution) of dichloromethane solution containing 16.31 g of 3-trifluoromethylpyridine N-oxide. Thereto, 12.69 g of oxalyl chloride was added dropwise at ⁇ 30 to ⁇ 20 ° C. and reacted at the same temperature for 1 hour. A mixed solution of 10.12 g of triethylamine and 10.82 g of dichloromethane was added dropwise to the reaction solution at ⁇ 30 to ⁇ 20 ° C. over 1 hour, and the mixture was further reacted at the same temperature for 2 hours. The reaction mixture was analyzed by liquid chromatography.
- 2-chloro-3-trifluoromethylpyridine can be produced with a high production rate and a high yield.
Abstract
Description
非特許文献1には、3-エトキシカルボニルピリジン N-オキシドとオキシ塩化リンとを反応させて2-クロロ-3-ピリジンカルボン酸エチルを製造する方法が記載されているが、2-クロロ-3-トリフルオロメチルピリジンの製造方法については記載されていない。
即ち本発明は、3-トリフルオロメチルピリジン N-オキシドと塩素化剤とを反応させることを特徴とする、2-クロロ-3-トリフルオロメチルピリジン又はその塩の製造方法、また、3-トリフルオロメチルピリジンを酸化して3-トリフルオロメチルピリジン N-オキシドを製造し、次いで得られた3-トリフルオロメチルピリジン N-オキシドと塩素化剤とを反応させることを特徴とする、2-クロロ-3-トリフルオロメチルピリジン又はその塩の製造方法に関する。
また、塩基を用いる場合、塩基と塩素化剤は任意の順序で添加することができる。例えば、塩基は塩素化剤を添加する前又は後に添加してもよく、塩素化剤と同時に添加してもよい。特に塩基を用いる場合、塩素化剤を添加した後に塩基を添加すると、2-クロロ-3-トリフルオロメチルピリジンの生成率、収率が顕著に向上する。
実施例1
(1)攪拌器、温度計及び冷却管を備えた四ツ口フラスコに、3-トリフルオロメチルピリジン147.0gと酢酸367.75gを仕込んだ。そこへ20~30℃で30%過酸化水素水141.71gを投入し、80~90℃で7時間反応させた。
反応液を冷却後、30℃以下で亜硫酸ナトリウム31.51gを添加した。添加後30~40℃で3時間攪拌し、反応液中の過剰の過酸化水素の処理が完了していることをヨウ化カリウムデンプン紙により確認した。
反応液を減圧下(15mmHg)で内温が50℃に達するまで加熱し、酢酸を留去した。そこへ水441mLを投入し、20℃以下で30%水酸化ナトリウム水溶液204.26gを滴下し、pH8.0に調整した。その後、1,2-ジクロロエタン275.6gによる保温抽出を50℃で3回繰り返し、3-トリフルオロメチルピリジン N-オキシド(融点76.0℃)158.16gを含む1,2-ジクロロエタン溶液985.0gを得た。
反応液を10℃以下で氷水24.45gに投入し、10~20℃で30分間攪拌した後分液した。得られた有機層を水洗し、2-クロロ-3-トリフルオロメチルピリジンを含む1,2-ジクロロエタン溶液43.1gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2-クロロ-3-トリフルオロメチルピリジン4.25gを含むことを確認した。
攪拌器、温度計及び乾燥管を備えた四ツ口フラスコに、3-トリフルオロメチルピリジン N-オキシド32.62gとオキシ塩化リン46.0gを仕込み、105~110℃で2時間反応させ、次いで120~125℃で5時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3-トリフルオロメチルピリジン N-オキシドを0.16%、2-クロロ-3-トリフルオロメチルピリジンを50.34%、2-クロロ-5-トリフルオロメチルピリジンを25.34%の割合で含むことを確認した。
反応液を減圧下(100mmHg)で内温が75℃に達するまで加熱し、過剰分のオキシ塩化リンを留去した。反応液を氷水163.1gに投入し、30℃以下で1時間攪拌した。その後、1,2-ジクロロエタンで抽出し、30分間攪拌して分液した。得られた有機層を水洗し、2-クロロ-3-トリフルオロメチルピリジンを含む1,2-ジクロロエタン溶液132.11gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2-クロロ-3-トリフルオロメチルピリジン13.17gを含むことを確認した。
(1)攪拌器、温度計及び冷却管を備えた四ツ口フラスコに、3-トリフルオロメチルピリジン238.63gと酢酸596.57gを仕込んだ。そこへ20~30℃で30%過酸化水素水229.85gを投入し、80~90℃で7時間反応させた。
反応液を冷却後、30℃以下で亜硫酸ナトリウム51.11gを添加した。添加後30~40℃で3時間攪拌し、反応液中の過剰の過酸化水素の処理が完了していることをヨウ化カリウムデンプン紙により確認した。
反応液を減圧下(15mmHg)で内温が55℃に達するまで加熱し、酢酸を留去した。そこへ水357.9mLを投入し、15℃以下で30%水酸化ナトリウム水溶液343.2gを滴下し、pH8.0に調整した。その後、ジクロロメタン633.1gによる保温抽出を30~40℃で2回繰り返した。次に、ジクロロメタン抽出溶液を常圧下で内温が50℃に達するまで加熱してジクロロメタンを留去すると共に系内の水分を除去し、3-トリフルオロメチルピリジン N-オキシド(融点76.0℃)259.57gを含むジクロロメタン溶液811.9gを得た。
反応液を10℃以下で氷水1019.3gに投入し、10~20℃で1時間攪拌した後分液した。得られた有機層に水407.8gを投入し、20~30℃で30%水酸化ナトリウム水溶液26.7gを滴下してpH8.0に調整し、同温度で2時間攪拌した。その後、分液し2-クロロ-3-トリフルオロメチルピリジンを含むジクロロメタン溶液1531gを得た。得られた溶液から常圧でジクロロメタンを留去し、内温が90℃に到達するまで加熱した後、減圧下(38mmHg)で内温が100℃に到達するまでの留分を収集して、純度99.27%の2-クロロ-3-トリフルオロメチルピリジン161.27gを得た。
攪拌器、温度計、乾燥管及び滴下漏斗を備えた四ツ口フラスコに、3-トリフルオロメチルピリジン N-オキシド3.26gを含む1,2-ジクロロエタン溶液23.65g(13.78%溶液)を仕込んだ。そこへ0~5℃で塩化オキサリル3.05gを滴下し、同温度で1時間反応させた。反応液に、0~10℃でトリエチルアミン2.42g及び1,2-ジクロロエタン4.08gの混合溶液を1時間要して滴下し、同温度で2時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3-トリフルオロメチルピリジン N-オキシドを39.72%、2-クロロ-3-トリフルオロメチルピリジンを54.63%、2-クロロ-5-トリフルオロメチルピリジンを1.31%の割合で含むことを確認した。
攪拌器、温度計、乾燥管及び滴下漏斗を備えた四ツ口フラスコに、3-トリフルオロメチルピリジン N-オキシド16.31gを含むジクロロメタン溶液124.49g(13.10%溶液)を仕込んだ。そこへ-30~-20℃で塩化オキサリル12.69gを滴下し、同温度で1時間反応させた。反応液に、-30~-20℃でトリエチルアミン10.12g及びジクロロメタン10.82gの混合溶液を1時間要して滴下し、同温度で2時間さらに反応させた。反応液を液体クロマトグラフィーで分析し、3-トリフルオロメチルピリジン N-オキシドを5.47%、2-クロロ-3-トリフルオロメチルピリジンを85.57%、2-クロロ-5-トリフルオロメチルピリジンを0.42%の割合で含むことを確認した。
反応液を10℃以下で氷水81.55gに投入し、10~20℃で1時間攪拌した後分液した。得られた有機層を水洗し、2-クロロ-3-トリフルオロメチルピリジンを含むジクロロメタン溶液143.25gを得た。得られた溶液を液体クロマトグラフィーで分析し、当該溶液中に2-クロロ-3-トリフルオロメチルピリジン14.18gを含むことを確認した。
なお、本出願は、2009年12月25日付で出願された日本特許出願(特願2009-293768号)に基づいており、その全体が引用により援用される。
また、ここに引用されるすべての参照は全体として取り込まれる。
Claims (6)
- 3-トリフルオロメチルピリジン N-オキシドと塩素化剤とを反応させることを特徴とする、2-クロロ-3-トリフルオロメチルピリジン又はその塩の製造方法。
- 3-トリフルオロメチルピリジンを酸化して3-トリフルオロメチルピリジン N-オキシドを製造し、次いで得られた3-トリフルオロメチルピリジン N-オキシドと塩素化剤とを反応させることを特徴とする、2-クロロ-3-トリフルオロメチルピリジン又はその塩の製造方法。
- 塩素化剤が塩化オキサリル及びオキシ塩化リンからなる群より選ばれる少なくとも1種である請求項1又は2の方法。
- 塩素化剤が塩化オキサリルである請求項1又は2の方法。
- 3-トリフルオロメチルピリジン N-オキシド1モルに対し、塩素化剤を1~10倍モル使用する請求項1又は2の方法。
- 3-トリフルオロメチルピリジン N-オキシドと塩素化剤との反応を、塩素化剤として塩化オキサリルを用い、-40℃~20℃の反応温度で行う、請求項1又は2の方法。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020127015827A KR101668144B1 (ko) | 2009-12-25 | 2010-12-22 | 2-클로로-3-트리플루오로메틸피리딘의 제조 방법 |
BR112012015701-9A BR112012015701B1 (pt) | 2009-12-25 | 2010-12-22 | processos para produzir 2-cloro-3-trifluorometilpiridina |
EP10839526.0A EP2520569B1 (en) | 2009-12-25 | 2010-12-22 | Processes for producing 2-chloro-3-trifluoromethylpyridine |
CN201080059179.8A CN102712590B (zh) | 2009-12-25 | 2010-12-22 | 2-氯-3-三氟甲基吡啶的生产方法 |
US13/518,584 US8691997B2 (en) | 2009-12-25 | 2010-12-22 | Processes for producing 2-chloro-3-trifluoromethylpyridine |
IL220520A IL220520A (en) | 2009-12-25 | 2012-06-19 | Processes for the production of 2-chloro-3-trifluoromethylpyridine |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009-293768 | 2009-12-25 | ||
JP2009293768 | 2009-12-25 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2011078296A1 true WO2011078296A1 (ja) | 2011-06-30 |
Family
ID=44195821
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2010/073252 WO2011078296A1 (ja) | 2009-12-25 | 2010-12-22 | 2-クロロ-3-トリフルオロメチルピリジンの製造方法 |
Country Status (8)
Country | Link |
---|---|
US (1) | US8691997B2 (ja) |
EP (1) | EP2520569B1 (ja) |
JP (1) | JP5702595B2 (ja) |
KR (1) | KR101668144B1 (ja) |
CN (1) | CN102712590B (ja) |
BR (1) | BR112012015701B1 (ja) |
IL (1) | IL220520A (ja) |
WO (1) | WO2011078296A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103601671B (zh) * | 2013-10-22 | 2016-08-17 | 上海泰坦科技股份有限公司 | 碘代三氟甲基吡啶的制备方法 |
JP6977174B2 (ja) * | 2018-01-05 | 2021-12-08 | 浙江▲藍▼天▲環▼保高科技股▲ふん▼有限公司 | 2−クロロ−5−トリフルオロメチルピリジンの作製方法 |
CN108409643A (zh) * | 2018-02-07 | 2018-08-17 | 南京红太阳生物化学有限责任公司 | 一种2-氯-3-三氯甲基吡啶的合成方法 |
CN113717095A (zh) * | 2021-07-15 | 2021-11-30 | 山东汇盟生物科技股份有限公司 | 一种制备2-氯-3-三氟甲基吡啶和2-氯-5-三氟甲基吡啶的方法 |
CN115784977A (zh) * | 2023-02-06 | 2023-03-14 | 淄博新农基作物科学有限公司 | 2-氯-3-三氟甲基吡啶的合成工艺 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5581860A (en) * | 1978-12-07 | 1980-06-20 | Ici Ltd | Chlorination |
JPS55122762A (en) | 1979-03-16 | 1980-09-20 | Ishihara Sangyo Kaisha Ltd | Production of chloro-3-trifluoromethylpyridine |
JP2009531439A (ja) * | 2006-03-27 | 2009-09-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 前立腺癌およびアンドロゲン受容体関連病態の治療のためのアンドロゲン受容体の調節剤 |
JP2009293768A (ja) | 2008-06-09 | 2009-12-17 | Bridgestone Corp | ストラットマウント |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0013474B1 (en) | 1978-12-07 | 1983-06-29 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-trifluoromethylpyridine |
JPS5659757A (en) * | 1979-10-22 | 1981-05-23 | Ishihara Sangyo Kaisha Ltd | Preparation of 2-chloro-5-trifluoromethylpyridine |
AU548249B2 (en) * | 1981-05-13 | 1985-12-05 | Imperial Chemical Industries Plc | Production of 3-trichloromethyl and 3-trifluoro methyl- pyridines |
DE3800179A1 (de) | 1988-01-07 | 1989-07-20 | Bayer Ag | Verfahren zur herstellung von 2-chlor-5-methyl-pyridin |
JP3291345B2 (ja) | 1993-01-27 | 2002-06-10 | 広栄化学工業株式会社 | 2−クロロ−3−シアノピリジンの製造法 |
-
2010
- 2010-12-21 JP JP2010284115A patent/JP5702595B2/ja active Active
- 2010-12-22 CN CN201080059179.8A patent/CN102712590B/zh active Active
- 2010-12-22 US US13/518,584 patent/US8691997B2/en active Active
- 2010-12-22 WO PCT/JP2010/073252 patent/WO2011078296A1/ja active Application Filing
- 2010-12-22 BR BR112012015701-9A patent/BR112012015701B1/pt active IP Right Grant
- 2010-12-22 KR KR1020127015827A patent/KR101668144B1/ko active IP Right Grant
- 2010-12-22 EP EP10839526.0A patent/EP2520569B1/en active Active
-
2012
- 2012-06-19 IL IL220520A patent/IL220520A/en active IP Right Grant
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5581860A (en) * | 1978-12-07 | 1980-06-20 | Ici Ltd | Chlorination |
US4393214A (en) | 1978-12-07 | 1983-07-12 | Imperial Chemical Industries Plc | Preparation of 2-chloro-5-trifluoromethylpyridine and 2-chloro-5-perchlorofluoromethylpyridines |
JPS55122762A (en) | 1979-03-16 | 1980-09-20 | Ishihara Sangyo Kaisha Ltd | Production of chloro-3-trifluoromethylpyridine |
JP2009531439A (ja) * | 2006-03-27 | 2009-09-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 前立腺癌およびアンドロゲン受容体関連病態の治療のためのアンドロゲン受容体の調節剤 |
JP2009293768A (ja) | 2008-06-09 | 2009-12-17 | Bridgestone Corp | ストラットマウント |
Non-Patent Citations (3)
Title |
---|
CHEM. PHARM. BULL., vol. 36, no. 6, 1988, pages 2244 - 2247 |
See also references of EP2520569A4 |
YAMANAKA, H. ET AL.: "Site-Selectivity in the Reaction of 3-Substituted Pyridine 1-Oxides with Phosphoryl Chloride", CHEM. PHARM. BULL., vol. 36, no. 6, 1988, pages 2244 - 2247 * |
Also Published As
Publication number | Publication date |
---|---|
CN102712590B (zh) | 2014-04-30 |
US20120259125A1 (en) | 2012-10-11 |
KR20120120171A (ko) | 2012-11-01 |
CN102712590A (zh) | 2012-10-03 |
IL220520A (en) | 2016-05-31 |
KR101668144B1 (ko) | 2016-10-20 |
EP2520569A4 (en) | 2013-06-05 |
EP2520569A1 (en) | 2012-11-07 |
EP2520569B1 (en) | 2014-03-26 |
BR112012015701A2 (pt) | 2015-09-15 |
BR112012015701B1 (pt) | 2021-04-20 |
JP2011148779A (ja) | 2011-08-04 |
IL220520A0 (en) | 2012-08-30 |
US8691997B2 (en) | 2014-04-08 |
JP5702595B2 (ja) | 2015-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5702595B2 (ja) | 2−クロロ−3−トリフルオロメチルピリジンの製造方法 | |
KR101421862B1 (ko) | 함질소 복소 고리 화합물 및 그 제조 방법 | |
TWI695824B (zh) | 製備3-氯-2-乙烯基苯基磺酸酯之方法 | |
EP2931047B1 (en) | Process for the preparation of 4-amino-5-fluoro-3-chloro-6-(substituted)picolinates | |
TWI648254B (zh) | Method for producing pest control agent and intermediate thereof | |
CN110520411A (zh) | 吡啶化合物的制造方法 | |
JP2009235062A (ja) | 3−アミノ−2−クロロ−6−トリフルオロメチルピリジンの製造方法 | |
JP6741028B2 (ja) | ベンゾオキサゾール化合物の製造方法 | |
JP6528772B2 (ja) | 3−(アルキルスルホニル)ピリジン−2−カルボン酸の製造方法 | |
JP2016084346A (ja) | ビス(3−フェネチルオキシフェニル)ジスルフィド誘導体およびその製造方法 | |
JP4698991B2 (ja) | ピリジルメチルカルバミン酸エステル化合物、その製造方法及びピリジルメチルアミン化合物の製造方法 | |
RU2702121C1 (ru) | Способ получения производного бензилового эфира 2-аминоникотиновой кислоты | |
EP1789383A1 (de) | Chirale 3-halophthalsäure-derivate | |
KR100371590B1 (ko) | 2-클로로피리딘의 제조방법 | |
WO2020158773A1 (ja) | ピリドン化合物の製造方法 | |
WO2019167814A1 (ja) | メルカプトフェノール化合物の製造方法及びその中間体 | |
JP2006137693A (ja) | 2−アシルオキシ−3−(4−テトラヒドロピラニル)−3−アミノ−2−プロペン酸エステルのカルボン酸塩及びその製法 | |
JP2016084347A (ja) | 置換フェニルエーテル化合物の製造方法 | |
JP2007246476A (ja) | ジオキサジニルピラゾール化合物の製造方法および中間体 | |
JPH05294931A (ja) | 新規中間体及び2−クロロ−5−(アミノメチル)ピリジンの製造方法 | |
JP2011162465A (ja) | ベンゾイソチアゾリノン−1−オキシド化合物の製造方法 | |
JPH10237048A (ja) | ケトン類の製造法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201080059179.8 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10839526 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 20127015827 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 220520 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13518584 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 5542/CHENP/2012 Country of ref document: IN Ref document number: 2010839526 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112012015701 Country of ref document: BR |
|
NENP | Non-entry into the national phase |
Ref country code: JP |
|
ENP | Entry into the national phase |
Ref document number: 112012015701 Country of ref document: BR Kind code of ref document: A2 Effective date: 20120625 |