JPH05310698A - Production of 3-amino-cycloalkyloxypyridine - Google Patents
Production of 3-amino-cycloalkyloxypyridineInfo
- Publication number
- JPH05310698A JPH05310698A JP4120947A JP12094792A JPH05310698A JP H05310698 A JPH05310698 A JP H05310698A JP 4120947 A JP4120947 A JP 4120947A JP 12094792 A JP12094792 A JP 12094792A JP H05310698 A JPH05310698 A JP H05310698A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- formula
- cycloalkyloxypyridine
- nitropyridine
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 6
- 238000010531 catalytic reduction reaction Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 11
- 239000002904 solvent Substances 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 4
- OZDPBNWXHQSBEH-UHFFFAOYSA-N 6-chloro-2-cyclohexyloxy-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1OC1CCCCC1 OZDPBNWXHQSBEH-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002221 antipyretic Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- XQNDUQYCYFNVSQ-UHFFFAOYSA-N 2-cyclohexyloxypyridin-3-amine Chemical compound NC1=CC=CN=C1OC1CCCCC1 XQNDUQYCYFNVSQ-UHFFFAOYSA-N 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 230000000202 analgesic effect Effects 0.000 abstract 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 2
- 230000001754 anti-pyretic effect Effects 0.000 abstract 2
- 239000003814 drug Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- -1 sulfonamide pyridine compound Chemical class 0.000 description 5
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- QLILRKBRWXALIE-UHFFFAOYSA-N 3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1 QLILRKBRWXALIE-UHFFFAOYSA-N 0.000 description 2
- LGRNLDNEOWKJDQ-UHFFFAOYSA-N CS(=O)(=O)NC1=CC=CN=C1OC1CCCCC1 Chemical compound CS(=O)(=O)NC1=CC=CN=C1OC1CCCCC1 LGRNLDNEOWKJDQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 1
- SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 1
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- DHLQICSNIQLOBU-UHFFFAOYSA-N CS(=O)(=O)NC1=CC=C([N+]([O-])=O)N=C1OC1CCCCC1 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)N=C1OC1CCCCC1 DHLQICSNIQLOBU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- GGZRVXCSRWTOME-UHFFFAOYSA-N pyridine;toluene Chemical compound C1=CC=NC=C1.CC1=CC=CC=C1 GGZRVXCSRWTOME-UHFFFAOYSA-N 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
【発明の詳細な説明】Detailed Description of the Invention
【０００１】[0001]
【産業上の利用分野】本発明は、特願平３―２８４２６
７号公報に記載されている解熱剤、鎮痛剤、抗炎症剤な
どとして有用なスルホンアミドピリジン化合物の合成原
料として重要な中間体３−アミノ―２―シクロアルキル
オキシピリジンの製造方法に関する。FIELD OF THE INVENTION The present invention relates to Japanese Patent Application No. 3-28426.
The present invention relates to a method for producing an intermediate 3-amino-2-cycloalkyloxypyridine which is important as a raw material for synthesizing a sulfonamide pyridine compound useful as an antipyretic agent, an analgesic agent, an anti-inflammatory agent, etc.
【０００２】[0002]
【従来の技術】３−アミノ―２―シクロアルキルオキシ
ピリジンの製造方法としては、本発明者らが、特願平３
―２８４２６７号公報において、２―シクロアルキルオ
キシ―３―ニトロピリジンを還元する方法を記載してい
る。2. Description of the Related Art As a method for producing 3-amino-2-cycloalkyloxypyridine, the present inventors have proposed Japanese Patent Application No.
-284267 describes a method for reducing 2-cycloalkyloxy-3-nitropyridine.
【０００３】しかし、６―クロロ―２―シクロアルキル
オキシ―３―ニトロピリジンを還元することにより製造
する方法は知られていない。However, a method for producing 6-chloro-2-cycloalkyloxy-3-nitropyridine by reduction is not known.
【０００４】[0004]
【発明が解決しようとする課題】従来の特願平３―２８
４２６７号公報に記載した２―シクロアルキルオキシ―
３―ニトロピリジンの還元する３−アミノ―２―シクロ
アルキルオキシピリジンの製造方法では、２―クロロ―
３―ニトロピリジンを出発原料として用いているが、こ
の化合物は２―クロロピリジンをニトロ化することによ
り得られる目的の２―クロロ―３―ニトロピリジンと主
生成物として得られる２―クロロ―５―ニトロピリジン
を分離精製することにより製造しているため、大量の製
造方法としては問題があった。[Patent Document 1] Japanese Patent Application No. 3-28
2-Cycloalkyloxy-described in Japanese Patent No. 4267
In the method for producing 3-amino-2-cycloalkyloxypyridine, which reduces 3-nitropyridine, 2-chloro-
Although 3-nitropyridine was used as a starting material, this compound was obtained by nitrating 2-chloropyridine, the desired 2-chloro-3-nitropyridine and 2-chloro-5 obtained as the main product. -Since it is produced by separating and refining nitropyridine, there is a problem as a large-scale production method.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、上記課題
の解決を目的に鋭意検討し、安価で入手可能な２，６−
ジクロロピリジンを出発原料として用いる以下の反応経
路に示す製造方法を検討し、２，６−ジクロロピリジン
より簡便な方法で製造できる６―クロロ―２―シクロア
ルキルオキシ―３―ニトロピリジン（特願平３―２８４
２６７号公報に記載）の接触還元により３−アミノ―２
―シクロアルキルオキシピリジンが簡便かつ高収率で得
られることを見い出し、本発明を完成した。DISCLOSURE OF THE INVENTION The inventors of the present invention have made earnest studies for the purpose of solving the above-mentioned problems, and have an inexpensive 2,6-
By examining the production method shown in the following reaction route using dichloropyridine as a starting material, 6-chloro-2-cycloalkyloxy-3-nitropyridine which can be produced by a simpler method than 2,6-dichloropyridine (Patent application 3-284
No. 267), 3-amino-2
The present invention has been completed by finding that cycloalkyloxypyridine can be easily obtained in high yield.
【０００６】〈反応経路〉 <Reaction Path>
【０００７】すなわち本発明は、式Ｉ That is, the present invention provides formula I
【０００８】（式中、Ｒは炭素原子数３〜８個のシクロ
アルキル基を表す。）で示される６―クロロ―２―シク
ロアルキルオキシ―３―ニトロピリジンをパラジウム―
炭素触媒存在下、加圧および／または加熱条件により接
触還元を行い、(In the formula, R represents a cycloalkyl group having 3 to 8 carbon atoms.) 6-chloro-2-cycloalkyloxy-3-nitropyridine represented by palladium-
In the presence of a carbon catalyst, catalytic reduction is performed under pressure and / or heating conditions,
【０００９】式ＩＩ Formula II
【００１０】（式中、Ｒは前記と同意義である。）で示
される３−アミノ―２―シクロアルキルオキシピリジン
を得ることを特徴とする３−アミノ―２―シクロアルキ
ルオキシピリジンの製造方法および、A method for producing 3-amino-2-cycloalkyloxypyridine, characterized in that 3-amino-2-cycloalkyloxypyridine represented by the formula (wherein R has the same meaning as defined above) is obtained. and,
【００１１】式Ｉで示される６―クロロ―２―シクロア
ルキルオキシ―３―ニトロピリジンをヒドラジンおよび
パラジウム―炭素触媒存在下接触還元を行うことにより
式ＩＩで示される３−アミノ―２―シクロアルキルオキ
シピリジンを得ることを特徴とする３−アミノ―２―シ
クロアルキルオキシピリジンの製造方法である。3-Amino-2-cycloalkyl represented by the formula II is obtained by catalytically reducing 6-chloro-2-cycloalkyloxy-3-nitropyridine represented by the formula I in the presence of hydrazine and a palladium-carbon catalyst. A method for producing 3-amino-2-cycloalkyloxypyridine, which comprises obtaining oxypyridine.
【００１２】以下、本発明の製造方法を説明する。The manufacturing method of the present invention will be described below.
【００１３】本発明における接触還元とは、パラジウ
ム、白金、ラネーニッケル、ロジウム等の金属またはそ
の塩類を触媒として用い、水素、ヒドラジン、メチルヒ
ドラジン等のヒドラジン誘導体、シクロヘキセン等で還
元する方法である。The catalytic reduction in the present invention is a method in which a metal such as palladium, platinum, Raney nickel, rhodium or a salt thereof is used as a catalyst and hydrogen, hydrazine, a hydrazine derivative such as methylhydrazine, cyclohexene or the like is used for reduction.
【００１４】本反応は、水、酢酸、メタノール、エタノ
ール、イソプロパノール、酢酸エチル、ジオキサン、テ
トラヒドロフラン、ベンゼン、キシレン、ヘキサン、シ
クロヘキセン等の溶媒中において、室温から溶媒の沸点
で、好ましくは５０℃から各溶媒の沸点までの反応温度
において行うことができる。本反応は塩酸、硫酸等の酸
の添加、また水素を用いる場合は、加圧下で行うことに
より反応を促進することができる。This reaction is carried out in a solvent such as water, acetic acid, methanol, ethanol, isopropanol, ethyl acetate, dioxane, tetrahydrofuran, benzene, xylene, hexane or cyclohexene at room temperature to the boiling point of the solvent, preferably from 50 ° C. It can be carried out at reaction temperatures up to the boiling point of the solvent. This reaction can be promoted by adding an acid such as hydrochloric acid or sulfuric acid, or under pressure when hydrogen is used.
【００１５】[0015]
【発明の効果】本発明により、Ｎ−（２―シクロアルキ
ルオキシ―３―ピリジル）メタンスルホンアミドを高収
率で、簡便に製造することが可能になり、解熱、鎮痛、
抗炎症剤などとして有用なスルホンアミドピリジン化合
物の合成原料の重要な中間体の工業的な提供が可能とな
った。INDUSTRIAL APPLICABILITY According to the present invention, it becomes possible to easily produce N- (2-cycloalkyloxy-3-pyridyl) methanesulfonamide in high yield, and to reduce fever, analgesia,
It has become possible to industrially provide an important intermediate for a synthetic raw material of a sulfonamide pyridine compound useful as an anti-inflammatory agent and the like.
【００１６】[0016]
【実施例】次に、実施例および参考例を挙げ本発明を更
に詳細に説明する。EXAMPLES Next, the present invention will be described in more detail with reference to Examples and Reference Examples.
【００１７】実施例１ （１）６―クロロ―シクロヘキシルオキシ―３―ニトロ
ピリジンの製造 ２，６―ジクロロ―３―ニトロピリジン１９．３ｇおよ
びシクロヘキサノール１５．０ｇを含むトルエン１８０
ｍｌ溶液に、反応温度を２０〜３０℃に保ちながら、粉
末の水酸化ナトリウム２０．０ｇを１５分間かけて加え
た。Example 1 (1) 6-chloro-cyclohexyloxy-3-nitro
Preparation of pyridine Toluene 180 containing 19.3 g of 2,6-dichloro-3-nitropyridine and 15.0 g of cyclohexanol
20.0 g of powdered sodium hydroxide was added to the ml solution over 15 minutes while maintaining the reaction temperature at 20 to 30 ° C.
【００１８】室温で４時間攪拌した後、水を加え、トル
エンで抽出、トルエン層を水洗、無水硫酸マグネシウム
で乾燥した。溶媒を濃縮して得られた残渣をトルエン―
ｎ―ヘキサンで再結晶することにより、６―クロロ―２
−シクロヘキシルオキシ―３―ニトロピリジン１７．１
ｇを得た。After stirring at room temperature for 4 hours, water was added and the mixture was extracted with toluene. The toluene layer was washed with water and dried over anhydrous magnesium sulfate. The residue obtained by concentrating the solvent is toluene-
By recrystallizing with n-hexane, 6-chloro-2
-Cyclohexyloxy-3-nitropyridine 17.1
g was obtained.
【００１９】ｍ．ｐ．７７〜７９℃M. p. 77-79 ° C
【００２０】（２）３―アミノ―２―シクロヘキシルオ
キシピリジンの製造 ６―クロロ―２−シクロヘキシルオキシ―３―ニトロピ
リジン２．６ｇを含むエタノール２５ｍｌ溶液に、８０
％ヒドラジン水溶液５．１ｍｌおよび５％パラジウム―
炭素０．２６ｇを加え３時間還流した。(2) 3-amino-2-cyclohexyl
Preparation of xypyridine In a 25 ml ethanol solution containing 2.6 g of 6-chloro-2-cyclohexyloxy-3-nitropyridine, 80
% Hydrazine aqueous solution 5.1 ml and 5% palladium-
Carbon (0.26 g) was added and the mixture was refluxed for 3 hours.
【００２１】反応液を室温に戻した後、パラジウム―炭
素を濾過して除き、濾液を濃縮、エタノールより再結晶
することにより無色針状晶の３―アミノ―２―シクロヘ
キシルオキシピリジン１．８ｇを得た。 ｍ．ｐ．６７〜６９℃After returning the reaction solution to room temperature, palladium-carbon was removed by filtration, the filtrate was concentrated and recrystallized from ethanol to give 1.8 g of 3-amino-2-cyclohexyloxypyridine as colorless needles. Obtained. m. p. 67-69 ° C
【００２２】参考例１ （１）Ｎ―（２―シクロヘキシルオキシ―３―ピリジ
ル）メタンスルホンアミドの製造 ３―アミノ―２―シクロヘキシルオキシピリジン１６．
８ｇを含むピリジン８８ｍｌ溶液に、氷冷下メタンスル
ホニルクロリド１１．０ｇを９分間かけて加え、同温度
で１５分間攪拌後、さらに室温で１時間攪拌した。反応
液に攪拌しながら水を加え、析出した結晶を濾取し、水
で洗浄した。Reference Example 1 (1) N- (2-cyclohexyloxy-3-pyridy
Preparation of methanesulfonamide 3-Amino-2-cyclohexyloxypyridine 16.
To 88 ml of a pyridine solution containing 8 g, 11.0 g of methanesulfonyl chloride was added over 9 minutes under ice cooling, and the mixture was stirred at the same temperature for 15 minutes, and further stirred at room temperature for 1 hour. Water was added to the reaction solution with stirring, and the precipitated crystals were collected by filtration and washed with water.
【００２３】得られた粗結晶をエタノール―ｎ―ヘキサ
ンで再結晶して無色プリズム晶のＮ―（２―シクロヘキ
シルオキシ―３―ピリジル）メタンスルホンアミド１
９．９ｇを得た。The obtained crude crystals were recrystallized from ethanol-n-hexane to give colorless prism crystals of N- (2-cyclohexyloxy-3-pyridyl) methanesulfonamide 1
9.9 g was obtained.
【００２４】ｍ．ｐ．１００〜１０２℃M. p. 100-102 ° C
【００２５】（２）Ｎ―（２―シクロヘキシルオキシ―
６―ニトロ―３―ピリジル）メタンスルホンアミドの製
造 Ｎ―（２―シクロヘキシルオキシ―３―ピリジル）メタ
ンスルホンアミド１９．５ｇを含む酢酸７２ｍｌ溶液
に、９５℃に加熱下６０％硝酸８．０ｇを２時間かけて
加え、さらに同温度で１時間攪拌した。反応液を室温に
戻し、攪拌しながら水を加え、析出した結晶を濾取し、
水で洗浄した。得られた粗結晶をジクロロメタンに溶解
し、飽和炭酸水素ナトリウム水溶液で洗浄後、無水硫酸
マグネシウムで乾燥した。溶媒を留去後、エタノールで
再結晶して淡黄色プリズム晶のＮ―（２―シクロヘキシ
ルオキシ―６―ニトロ―３―ピリジル）メタンスルホン
アミド１２．３ｇを得た。(2) N- (2-cyclohexyloxy-
Preparation of 6-nitro-3-pyridyl) methanesulfonamide
To 72 ml of acetic acid solution containing 19.5 g of N- (2-cyclohexyloxy-3-pyridyl) methanesulfonamide was added 8.0 g of 60% nitric acid under heating at 95 ° C over 2 hours, and further at the same temperature for 1 hour. It was stirred. The reaction solution was returned to room temperature, water was added with stirring, the precipitated crystals were collected by filtration,
It was washed with water. The obtained crude crystals were dissolved in dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to obtain 12.3 g of N- (2-cyclohexyloxy-6-nitro-3-pyridyl) methanesulfonamide as pale yellow prism crystals.
【００２６】ｍ．ｐ．１５５〜１５６℃M. p. 155-156 ° C
───────────────────────────────────────────────────── フロントページの続き (72)発明者 柏 真理子 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 (72)発明者 畑山 勝男 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Mariko Kashiwa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuo Hatayama 3-24-1 Takada, Toshima-ku, Tokyo Taisho Within Pharmaceuticals Co., Ltd.
Claims (2)
表す。）で示される６―クロロ―２―シクロアルキルオ
キシ―３―ニトロピリジンをパラジウム―炭素触媒存在
下、加圧および／または加熱条件により接触還元を行
い、式 （式中、Ｒは前記と同意義である。）で示される３−ア
ミノ―２―シクロアルキルオキシピリジンを得ることを
特徴とする３−アミノ―２―シクロアルキルオキシピリ
ジンの製造方法。1. A formula (In the formula, R represents a cycloalkyl group having 3 to 8 carbon atoms.) 6-chloro-2-cycloalkyloxy-3-nitropyridine represented by the formula: Or catalytic reduction is performed according to heating conditions, (In the formula, R has the same meaning as described above.) A 3-amino-2-cycloalkyloxypyridine is obtained, which is a process for producing 3-amino-2-cycloalkyloxypyridine.
表す。）で示される６―クロロ―２―シクロアルキルオ
キシ―３―ニトロピリジンをヒドラジンおよびパラジウ
ム―炭素触媒存在下接触還元を行うことにより、式 （式中、Ｒは前記と同意義である。）で示される３−ア
ミノ―２―シクロアルキルオキシピリジンを得ることを
特徴とする３−アミノ―２―シクロアルキルオキシピリ
ジンの製造方法。2. A formula (In the formula, R represents a cycloalkyl group having 3 to 8 carbon atoms.) 6-chloro-2-cycloalkyloxy-3-nitropyridine is subjected to catalytic reduction in the presence of hydrazine and a palladium-carbon catalyst. By doing the formula (In the formula, R has the same meaning as described above.) A 3-amino-2-cycloalkyloxypyridine is obtained, which is a process for producing 3-amino-2-cycloalkyloxypyridine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4120947A JPH05310698A (en) | 1992-05-14 | 1992-05-14 | Production of 3-amino-cycloalkyloxypyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4120947A JPH05310698A (en) | 1992-05-14 | 1992-05-14 | Production of 3-amino-cycloalkyloxypyridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05310698A true JPH05310698A (en) | 1993-11-22 |
Family
ID=14798912
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4120947A Pending JPH05310698A (en) | 1992-05-14 | 1992-05-14 | Production of 3-amino-cycloalkyloxypyridine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH05310698A (en) |
-
1992
- 1992-05-14 JP JP4120947A patent/JPH05310698A/en active Pending
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