JPS6059227B2 - N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine and its production method - Google Patents
N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine and its production methodInfo
- Publication number
- JPS6059227B2 JPS6059227B2 JP51068167A JP6816776A JPS6059227B2 JP S6059227 B2 JPS6059227 B2 JP S6059227B2 JP 51068167 A JP51068167 A JP 51068167A JP 6816776 A JP6816776 A JP 6816776A JP S6059227 B2 JPS6059227 B2 JP S6059227B2
- Authority
- JP
- Japan
- Prior art keywords
- lower alkyl
- pyrrolidine
- nitro
- formula
- nitromethylenepyrrolidine
- 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.)
- Expired
Links
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title claims description 15
- -1 alkylene pyrrolidine Chemical compound 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- GPRSTIIZOTUISG-UHFFFAOYSA-N 2-[2-(nitromethylidene)pyrrolidin-1-yl]ethanol Chemical compound OCCN1CCCC1=C[N+]([O-])=O GPRSTIIZOTUISG-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- LMDOTPWVWNPVEW-UHFFFAOYSA-N 3-[2-(nitromethylidene)pyrrolidin-1-yl]propan-1-ol Chemical compound OCCCN1CCCC1=C[N+]([O-])=O LMDOTPWVWNPVEW-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 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
- 230000003474 anti-emetic effect Effects 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- DZXBHDRHRFLQCJ-UHFFFAOYSA-M sodium;methyl sulfate Chemical compound [Na+].COS([O-])(=O)=O DZXBHDRHRFLQCJ-UHFFFAOYSA-M 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JSZOAYXJRCEYSX-UHFFFAOYSA-N 1-nitropropane Chemical compound CCC[N+]([O-])=O JSZOAYXJRCEYSX-UHFFFAOYSA-N 0.000 description 1
- YVTYKRYVHZTBPJ-UHFFFAOYSA-N 3-(2-oxopyrrolidin-1-yl)propyl acetate Chemical compound CC(=O)OCCCN1CCCC1=O YVTYKRYVHZTBPJ-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- HWBLTYHIEYOAOL-UHFFFAOYSA-N Diisopropyl sulfate Chemical compound CC(C)OS(=O)(=O)OC(C)C HWBLTYHIEYOAOL-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- RJFAYQIBOAGBLC-BYPYZUCNSA-N Selenium-L-methionine Chemical compound C[Se]CC[C@H](N)C(O)=O RJFAYQIBOAGBLC-BYPYZUCNSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- FEZBIKUBAYAZIU-UHFFFAOYSA-N trimethobenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCC=2C=CC(OCCN(C)C)=CC=2)=C1 FEZBIKUBAYAZIU-UHFFFAOYSA-N 0.000 description 1
- 229960004161 trimethobenzamide Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
【発明の詳細な説明】
この発明は、
一般式
（式中、Ｒ１は低級アルキル基、Ｒ２は水素原子または
直鎖状ないし分枝状の低級アルキル基をそれぞれ意味す
る。DETAILED DESCRIPTION OF THE INVENTION This invention is based on the general formula (wherein R1 means a lower alkyl group and R2 means a hydrogen atom or a linear or branched lower alkyl group, respectively.
）で示されるＮ−ヒドロキシ低級アルキルー２−ニトロ
低級アルキレンピロリジンおよびその製造法に関する。) N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine and its production method.
この発明による化合物〔■〕は新規化合物であつて、一
般式
（式中、Ｒ１は前記と同意義である。The compound [■] according to the present invention is a new compound, and has the general formula (wherein R1 has the same meaning as above).
）で示されるＮ−アセトキシ低級アルキルー２−オキソ
ピロリジンに、低級アルキル硫酸エステル、アルカリア
ルコレートおよびニトロ低級アルカンを反応させること
により得られる。) is obtained by reacting N-acetoxy lower alkyl-2-oxopyrrolidine with a lower alkyl sulfate, an alkali alcoholate, and a nitro lower alkane.
Ｒ１で示される低級アルキル基としては、エチル、プロ
ピルのようなＣ１〜５のようなアルキル基が例示され、
Ｒ２で示される低級アルキル基としては、メチル、エチ
ルのようなＣ１〜３のアルキル基が例示される。Examples of the lower alkyl group represented by R1 include C1-5 alkyl groups such as ethyl and propyl,
Examples of the lower alkyl group represented by R2 include C1-3 alkyl groups such as methyl and ethyl.
この発明の製造法において用いられる低級アルキル硫酸
エステルとしては、例えばジメチル硫酸、ジエチル硫酸
、ジプロピル硫酸、ジイソプロピル硫酸などが挙げられ
、またアルカリ金属アルコレートとしては、例えば、メ
タノール、エタノール、プロパノール、イソプロパノー
ル、ブタノールのようなアルコールを、ナトリウム、カ
リウムのようなアルカリ金属と反応させることによつて
形成されたものが挙げられ、またニトロ低級アルカンと
しては、ニトロメタン、ニトロエタン、ニトロプロパン
などが挙げられる。Examples of lower alkyl sulfates used in the production method of the present invention include dimethyl sulfate, diethyl sulfate, dipropyl sulfate, diisopropyl sulfate, etc., and examples of alkali metal alcoholates include methanol, ethanol, propanol, isopropanol, Examples include those formed by reacting alcohols such as butanol with alkali metals such as sodium and potassium, and nitro lower alkanes include nitromethane, nitroethane, nitropropane, and the like.
この発明による化合物（■）は、ついで還元されてＮ一
置換−２−アミノ低級アルキレンピロリジンに導かれる
。The compound (■) according to the invention is then reduced to give the N-monosubstituted-2-amino lower alkylene pyrrolidine.
この一連の反応の一例を反応式で示せば、次のとおりで
ある。式〔■〕で示されるこの発明による化合物は、式
で示される中間体から得られる。An example of this series of reactions is shown in the following reaction formula. The compounds according to the invention of the formula [■] are obtained from the intermediates of the formula.
さらに上記ピロリジン化合物〔■〕は、次の反応式のよ
うに、置換安息香酸ないしその反応性誘導体との反応に
より対応する置換ベンズアミド化合物に導かれる。Furthermore, the above-mentioned pyrrolidine compound [■] is led to the corresponding substituted benzamide compound by reaction with substituted benzoic acid or its reactive derivative, as shown in the following reaction formula.
この発明のよる反応は、アルコール類のようなこの反応
に悪影響を与えない溶媒中で行なわれることが多い。Reactions according to this invention are often carried out in solvents that do not adversely affect the reaction, such as alcohols.
また反応剤自身を溶媒として用いることもできる。反応
温度は特に限定されず、反応剤、溶媒の種類などにより
適宜選択される。Moreover, the reactant itself can also be used as a solvent. The reaction temperature is not particularly limited and is appropriately selected depending on the type of reactant and solvent.
この発明のよる化合物は、優れた治療学的活性、とりわ
け鎮吐作用を有する置換ベンズアミド化合物の合成中間
体として極めて有用の物質である。The compounds according to the present invention are extremely useful substances as intermediates for the synthesis of substituted benzamide compounds having excellent therapeutic activity, especially antiemetic activity.
この発明のよる化合物から導かれた置換ベンズアミド化
合物の代表例としては、Ｎ−（１−２″−ヒドロキシエ
チル）−２−ピロリジニルメチル）−２−メトキシー５
−エチルスルホニルベンズアミド、Ｎ−（１−（３″−
ヒドロキシプロピル）一２−ピロリジニルメチル）−２
−メトキシー５一エチルスルホニルベンズアミドおよび
Ｎ−（１一（３″−ヒドロキシプロピル）−２−ピロリ
ジニルメチル）−２−メトキシー５−スルファモイルベ
ンズアミドが挙げられ、これらは従来公知の鎮吐剤であ
るク町レプロマジン、プロクロルペラジンおよびトリメ
トベンズアミドに比べて、いずれも優れた鎮吐作用を有
することが確認されている。Representative examples of substituted benzamide compounds derived from the compounds of this invention include N-(1-2''-hydroxyethyl)-2-pyrrolidinylmethyl)-2-methoxy5
-ethylsulfonylbenzamide, N-(1-(3″-
Hydroxypropyl)-2-pyrrolidinylmethyl)-2
-methoxy-5-ethylsulfonylbenzamide and N-(1-(3''-hydroxypropyl)-2-pyrrolidinylmethyl)-2-methoxy5-sulfamoylbenzamide, which are conventionally known antiemetics. It has been confirmed that all of them have superior antiemetic effects compared to lepromazine, prochlorperazine, and trimethobenzamide.
この発明の技術的特徴を具体的に説明するため、この発
明のいくつかの実施例を示すが、この発明はこれらの操
作条件および適用に限定されるものではない。実施例１
Ｎ−（２−ヒドロキシエチル）−２−ニトロメチレンピ
ロリジン３′フラスコに、Ｎ−（２−アセトキシエチル
）−２−ピロリジン２６４Ｖを入れ、さらにジメＬチル
硫酸１９４ｙを滴下する。In order to specifically explain the technical features of this invention, some examples of this invention will be shown, but this invention is not limited to these operating conditions and applications. Example 1 N-(2-hydroxyethyl)-2-nitromethylenepyrrolidine 264V of N-(2-acetoxyethyl)-2-pyrrolidine is placed in a 3' flask, and 194y of dimethyl methyl sulfate is added dropwise.
得られた溶液を６０〜６３℃で１時間半加熱する。この
溶液を冷却し、ナトリウムエチレート溶液（無水エチル
アルコール１０８０ｍＬにナトリウム３５．５ダを溶か
して形成したもの）を１５℃の温度で加える。この混合
物を１時間ｊ攪拌し、次にニトロメタン１４１ｙを加え
る。さらにこの反応混合物を還流温度で５時間加熱する
。メチル硫酸ナトリウムを枦別した後、エチルアルコー
ルと酢酸エチルを蒸発させる。クロロホルムを添加し、
生じた沈殿物を淵別フし、溶媒の蒸発によつて得られた
油状物をジオキサン４５０ｍＬ中に溶解する。The resulting solution is heated at 60-63°C for 1.5 hours. The solution is cooled and a sodium ethylate solution (formed by dissolving 35.5 Da of sodium in 1080 mL of absolute ethyl alcohol) is added at a temperature of 15°C. The mixture is stirred for 1 hour, then 141y of nitromethane is added. The reaction mixture is further heated at reflux temperature for 5 hours. After separating off the sodium methyl sulfate, ethyl alcohol and ethyl acetate are evaporated. Add chloroform,
The precipitate formed is filtered off and the oil obtained by evaporation of the solvent is dissolved in 450 ml of dioxane.
得られた結晶を淵取し、洗浄して、乾燥する。Ｎ−（２
−ヒドロキシエチル）−２−ニトロメチレンピロリジン
１３２．６ｙが得られた（融点１２３〜１２４℃）。実
施例２
Ｎ−（３−ヒドロキシプロピル）−２−ニトロメチレン
ピロリジン２ｅのフラスコに、Ｎ−（３−アセトキシプ
ロピル）−２−ピロリジノン２８９ｆを入れ、ジメチル
硫酸１８５．６ｙを滴下する。The obtained crystals are filtered, washed and dried. N-(2
-Hydroxyethyl)-2-nitromethylenepyrrolidine 132.6y was obtained (melting point 123-124°C). Example 2 N-(3-acetoxypropyl)-2-pyrrolidinone 289f is placed in a flask containing N-(3-hydroxypropyl)-2-nitromethylenepyrrolidine 2e, and 185.6y of dimethyl sulfate is added dropwise.
この混合物を３時間半６０〜６５℃で加熱する。冷却後
、ナトリウムプロピレート溶液（プロピルアルコール中
にナトリウム３５．７ｆ１を加えて形成したもの）８５
０ｍ１を１７Ｃの温度で加える。この混合物を１時間攪
拌する。ニトロメタン１４１．３ｙを加え、４時間、５
０〜５５℃で加熱した後、メチル硫酸ナトリウムを枦別
し、溶媒であるプロピルアルコールならびに酢酸プロピ
ルを蒸発する。クロロホルム１７００ｍ１を加え、この
混合物を淵過する。This mixture is heated at 60-65° C. for 3 and a half hours. After cooling, sodium propylate solution (formed by adding 35.7 f1 of sodium in propyl alcohol) 85
Add 0 ml at a temperature of 17C. This mixture is stirred for 1 hour. Added 141.3y of nitromethane and heated for 4 hours, 5
After heating at 0 to 55°C, sodium methyl sulfate is separated off, and the solvents propyl alcohol and propyl acetate are evaporated. 1700 ml of chloroform are added and the mixture is filtered.
Claims (1)
は直鎖ないし分枝状の低級アルキル基をそれぞれ意味す
る。 ）で示されるＮ−ヒドロキシ低級アルキル−２−ニトロ
低級アルキレンピロリジン。 ２ Ｎ−（２−ヒドロキシエチル）−２−ニトロメチレ
ンピロリジンである特許請求の範囲第１項記載の化合物
。 ３ Ｎ−（３−ヒドロキシプロピル）−２−ニトロメチ
レンピロリジンである特許請求の範囲第１項記載の化合
物。 ４ 一般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＿１は低級アルキル基を意味する。 ）で示されるＮ−アセトキシ低級アルキル−２−オキソ
ピロリジンに、低級アルキル硫酸エステル、アルカリア
ルコレートおよびニトロ低級アルカンを反応させて、一
般式 ▲数式、化学式、表等があります▼ （式中Ｒ＿１は前記と同意義であり、Ｒ＿２は水素原子
または直鎖状ないし分枝状の低級アルキル基を意味する
。 ）で示されるＮ−ヒドロキシ低級アルキル−２−ニトロ
低級アルキレンピロリジンを得ることを特徴とするＮ−
ヒドロキシ低級アルキル−２−ニトロ低級アルキレンピ
ロリジンの製造法。 ５ Ｎ−（２−ヒドロキシエチル）−２−ニトロメチレ
ンピロリジンを合成するための特許請求の範囲第４項記
載の製造法。 ６ Ｎ−（３−ヒドロキシプロピル）−２−ニトロメチ
レンピロリジンを合成するための特許請求の範囲第４項
記載の製造法。[Claims] 1 General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 means a lower alkyl group, and R_2 means a hydrogen atom or a straight-chain or branched lower alkyl group, respectively.) The indicated N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine. 2. The compound according to claim 1, which is N-(2-hydroxyethyl)-2-nitromethylenepyrrolidine. 3. The compound according to claim 1, which is N-(3-hydroxypropyl)-2-nitromethylenepyrrolidine. 4 General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 means a lower alkyl group.) N-acetoxy lower alkyl-2-oxopyrrolidine, lower alkyl sulfate, alkali alcoholate and a nitro lower alkane are reacted to form the general formula ▲ mathematical formula, chemical formula, table, etc. ) N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine is obtained.
A method for producing hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine. 5. The manufacturing method according to claim 4 for synthesizing N-(2-hydroxyethyl)-2-nitromethylenepyrrolidine. The manufacturing method according to claim 4 for synthesizing 6 N-(3-hydroxypropyl)-2-nitromethylenepyrrolidine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7518175A FR2314177A1 (en) | 1975-06-09 | 1975-06-09 | NEW N-ALKANOL SUBSTITUTED HETEROCYCLIC AMINES, THEIR DERIVATIVES, THEIR METHODS OF PREPARATION |
| FR7518175 | 1975-06-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51149269A JPS51149269A (en) | 1976-12-22 |
| JPS6059227B2 true JPS6059227B2 (en) | 1985-12-24 |
Family
ID=9156325
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51068166A Granted JPS51149268A (en) | 1975-06-09 | 1976-06-09 | Nnalkanoll22substituted heterocyclic compounds and production thereof |
| JP51068167A Expired JPS6059227B2 (en) | 1975-06-09 | 1976-06-09 | N-hydroxy lower alkyl-2-nitro lower alkylene pyrrolidine and its production method |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51068166A Granted JPS51149268A (en) | 1975-06-09 | 1976-06-09 | Nnalkanoll22substituted heterocyclic compounds and production thereof |
Country Status (35)
| Country | Link |
|---|---|
| JP (2) | JPS51149268A (en) |
| AR (1) | AR211927A1 (en) |
| AT (1) | AT349456B (en) |
| AU (1) | AU504920B2 (en) |
| BE (1) | BE842058A (en) |
| BG (1) | BG24800A3 (en) |
| CA (1) | CA1077949A (en) |
| CH (1) | CH614939A5 (en) |
| CS (1) | CS188284B2 (en) |
| DD (1) | DD125072A5 (en) |
| DE (1) | DE2623000A1 (en) |
| DK (1) | DK251876A (en) |
| EG (1) | EG13867A (en) |
| ES (1) | ES448642A1 (en) |
| FI (1) | FI761641A7 (en) |
| FR (1) | FR2314177A1 (en) |
| GB (2) | GB1499708A (en) |
| HK (1) | HK63679A (en) |
| HU (1) | HU171835B (en) |
| IE (1) | IE43228B1 (en) |
| IL (1) | IL49595A (en) |
| IN (1) | IN141747B (en) |
| LU (1) | LU75097A1 (en) |
| MC (1) | MC1104A1 (en) |
| MW (1) | MW1576A1 (en) |
| NL (1) | NL188526C (en) |
| NO (1) | NO761886L (en) |
| OA (1) | OA05344A (en) |
| PH (1) | PH15172A (en) |
| PT (1) | PT65163B (en) |
| RO (1) | RO69253A (en) |
| SE (1) | SE410852B (en) |
| YU (1) | YU39966B (en) |
| ZA (1) | ZA763041B (en) |
| ZM (1) | ZM6476A1 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2684965A (en) * | 1950-08-10 | 1954-07-27 | Abbott Lab | Aminoalkylpiperidines |
-
1975
- 1975-06-09 FR FR7518175A patent/FR2314177A1/en active Granted
-
1976
- 1976-05-17 IL IL49595A patent/IL49595A/en unknown
- 1976-05-20 MC MC761197A patent/MC1104A1/en unknown
- 1976-05-21 BE BE1007403A patent/BE842058A/en not_active IP Right Cessation
- 1976-05-21 ZA ZA763041A patent/ZA763041B/en unknown
- 1976-05-22 DE DE19762623000 patent/DE2623000A1/en not_active Withdrawn
- 1976-05-24 AR AR263373A patent/AR211927A1/en active
- 1976-05-25 AU AU14259/76A patent/AU504920B2/en not_active Expired
- 1976-05-27 IN IN925/CAL/76A patent/IN141747B/en unknown
- 1976-05-28 YU YU1310/76A patent/YU39966B/en unknown
- 1976-06-01 IE IE1165/76A patent/IE43228B1/en unknown
- 1976-06-01 AT AT399876A patent/AT349456B/en not_active IP Right Cessation
- 1976-06-01 PT PT65163A patent/PT65163B/en unknown
- 1976-06-02 RO RO7686326A patent/RO69253A/en unknown
- 1976-06-03 NO NO761886A patent/NO761886L/no unknown
- 1976-06-03 ZM ZM64/76A patent/ZM6476A1/en unknown
- 1976-06-04 LU LU75097A patent/LU75097A1/xx unknown
- 1976-06-04 BG BG033361A patent/BG24800A3/en unknown
- 1976-06-04 CS CS763723A patent/CS188284B2/en unknown
- 1976-06-05 OA OA55841A patent/OA05344A/en unknown
- 1976-06-07 ES ES448642A patent/ES448642A1/en not_active Expired
- 1976-06-08 SE SE7606425A patent/SE410852B/en not_active IP Right Cessation
- 1976-06-08 DK DK251876A patent/DK251876A/en unknown
- 1976-06-08 GB GB18917/77A patent/GB1499708A/en not_active Expired
- 1976-06-08 GB GB23694/76A patent/GB1499707A/en not_active Expired
- 1976-06-09 DD DD193271A patent/DD125072A5/xx not_active IP Right Cessation
- 1976-06-09 HU HU76SO00001170A patent/HU171835B/en unknown
- 1976-06-09 FI FI761641A patent/FI761641A7/fi not_active Application Discontinuation
- 1976-06-09 NL NLAANVRAGE7606241,A patent/NL188526C/en not_active IP Right Cessation
- 1976-06-09 JP JP51068166A patent/JPS51149268A/en active Granted
- 1976-06-09 MW MW15/76A patent/MW1576A1/en unknown
- 1976-06-09 CH CH730176A patent/CH614939A5/en not_active IP Right Cessation
- 1976-06-09 CA CA254,481A patent/CA1077949A/en not_active Expired
- 1976-06-09 JP JP51068167A patent/JPS6059227B2/en not_active Expired
- 1976-06-20 EG EG325/76A patent/EG13867A/en active
-
1979
- 1979-09-06 HK HK636/79A patent/HK63679A/en unknown
-
1980
- 1980-04-25 PH PH23958A patent/PH15172A/en unknown
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