JPS6157579A - Preparation of 3-aminopyrrolidine or its salt - Google Patents

Preparation of 3-aminopyrrolidine or its salt

Info

Publication number
JPS6157579A
JPS6157579A JP17843884A JP17843884A JPS6157579A JP S6157579 A JPS6157579 A JP S6157579A JP 17843884 A JP17843884 A JP 17843884A JP 17843884 A JP17843884 A JP 17843884A JP S6157579 A JPS6157579 A JP S6157579A
Authority
JP
Japan
Prior art keywords
acid
aminopyrrolidine
formula
salt
compound
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.)
Granted
Application number
JP17843884A
Other languages
Japanese (ja)
Other versions
JPH0413339B2 (en
Inventor
Tetsuo Santo
山藤 哲夫
Hideyoshi Nagaki
長木 秀嘉
Hiroyasu Takagi
高木 宏育
Yoshinori Konishi
小西 義憲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toyama Chemical Co Ltd
Original Assignee
Toyama Chemical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Toyama Chemical Co Ltd filed Critical Toyama Chemical Co Ltd
Priority to JP17843884A priority Critical patent/JPS6157579A/en
Publication of JPS6157579A publication Critical patent/JPS6157579A/en
Publication of JPH0413339B2 publication Critical patent/JPH0413339B2/ja
Granted legal-status Critical Current

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  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for producing an antibacterial agent by a simple operation, by reacting a 1-alkoxycarbonyl-3- phthalimidopyrrolidine with a mineral acid. CONSTITUTION:A compound shown by the formula I (R<1> is lower alkyl) is reacted with a mineral acid such as conc. hydrochloric acid, conc. sulfuric acid, diluted sulfuric acid, etc. at 100-150 deg.C for 5-20hr to give 3-aminopyrrolidine. The compound shown by the formula I is proudced from a compound (e.g., 1-ethoxycarbonyl-3-pyridone) shown by the formula II by a method following the equation. Prepared 3-aminopyrrolidine is extremely useful as an intermediate for producing a quinolinecarboxylic acid and naphthyridinecarboxylic acid compound shown by the formula III (R<2> is lower alkyl, lower alkenyl, or phenyl; X is C, or N) suitable as an antibacterial agent.

Description

【発明の詳細な説明】 〔産業上の利用分野〕 本発明は3−アミノピロリジンまたはその塩の製造法に
関する。さらに詳細には、本発明は、−〔式中、几lは
低級アルキル基を示す。〕で表わされる化合物を鉱酸と
゛反応させることを特徴トスる3−アミノピロリジンま
たはその塩の製造法に関する。
DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 3-aminopyrrolidine or a salt thereof. More specifically, the present invention provides - [wherein ⇠l represents a lower alkyl group. The present invention relates to a method for producing 3-aminopyrrolidine or a salt thereof, which comprises reacting a compound represented by the following with a mineral acid.

本発明方法によって得られる3−アミノピロリジンまた
はその塩は、合成抗菌剤として有用な一般式(I[] NH。
3-Aminopyrrolidine or its salt obtained by the method of the present invention has the general formula (I[]NH) useful as a synthetic antibacterial agent.

で表わされるキノリ/カルボン酸およびナフチリジンカ
ルボン酸系化合物を製造する際の中間体として極めて有
用な化合物である。
It is an extremely useful compound as an intermediate in the production of quinoli/carboxylic acid and naphthyridine carboxylic acid compounds represented by

〔従来技術〕[Prior art]

従来、3−アミノピロリジンまたはその塩は、つぎに示
すルートに従って製造されている(ジャーナル・オブ・
メデイシナル・ケミストリー、第11巻、第1034〜
1037頁(1968年)iたは!!!f開昭53−2
8161号公報)。
Conventionally, 3-aminopyrrolidine or its salt has been produced according to the following route (Journal of
Medicinal Chemistry, Volume 11, No. 1034~
Page 1037 (1968) itaha! ! ! f Kaisho 53-2
Publication No. 8161).

〔発明が解決しようとする問題点〕[Problem that the invention seeks to solve]

しかしながら、上記した従来の方法によれば、ピロリジ
ンの1位をベンジル基で保護しているため、最終工程に
おいてこれを接触還元によシ脱離させる必要があるので
、この方法を工業的に実施することは極めて困難であっ
た。
However, according to the conventional method described above, since the 1-position of pyrrolidine is protected with a benzyl group, it is necessary to eliminate it by catalytic reduction in the final step, so this method cannot be implemented industrially. It was extremely difficult to do so.

〔問題を解決するための手段〕[Means to solve the problem]

かかる状況下において、本発明者らは、このような接触
還元を行うことなく、簡単な操作で工業的に有利な3−
アミノピロリジンまたはその塩の製造法を開発せんと鋭
意研究した結果、本発明を完成するに至った。
Under such circumstances, the present inventors have developed the industrially advantageous 3-
As a result of intensive research to develop a method for producing aminopyrrolidine or its salt, the present invention was completed.

本発明方法によれば、ピロリジン骨格の1位にRI Q
C−基(R1は前記と同様の意味を有する)を導入した
一般式CI)の化合物を原料とし、これと鉱酸を反応さ
せて1位および3位の保護基を同時に脱離させることに
よシ、容易に3−アミノピロリジンまたはその塩が得ら
れる。したがって、本発明方法は操作が簡単であるばか
υでなく、経済的にも優れ、工業的に有利な方法である
According to the method of the present invention, RI Q
By using a compound of the general formula CI) into which a C-group (R1 has the same meaning as above) as a raw material and reacting it with a mineral acid to simultaneously remove the protecting groups at the 1st and 3rd positions. 3-Aminopyrrolidine or its salt can be easily obtained. Therefore, the method of the present invention is not only easy to operate, but also economically superior and industrially advantageous.

以下、本発明方法を詳細に説明する。The method of the present invention will be explained in detail below.

なお、本明細書において、「低級アルキル基」とは、た
とえば、メチル、エチル、n−プロピル、イソプロピル
、n−ブチル、イソブチル、5ec−ブチル、tart
−ブチルなどの01〜4アルキル基を、および「低級ア
ルケニル基」とは、たとえば、ビニル、アリルなどのC
8〜4アルケニル基を意味するものとする。
In addition, in this specification, "lower alkyl group" includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 5ec-butyl, tart
-01-4 alkyl group such as butyl, and "lower alkenyl group" refers to C
8-4 alkenyl group shall be meant.

本発明方法における鉱酸としては、たとえば、徽塩酸、
濃硫酸、希硫酸などが挙げられ、これらは一般式CII
の化合物に対して約10〜50倍モル使用される。また
、本発明方法は、100〜150℃で5〜20時間反応
させることによって実施され、ついで、所望に応じて通
常の脱塩または塩形成反応を行ってもよい。
The mineral acids used in the method of the present invention include, for example, hydrochloric acid,
Concentrated sulfuric acid, diluted sulfuric acid, etc. are mentioned, and these have the general formula CII
It is used in an amount of about 10 to 50 times the molar amount of the compound. The method of the present invention is also carried out by reacting at 100-150° C. for 5-20 hours, followed by conventional desalting or salt-forming reactions, if desired.

3−アミノピロリジンの塩としては、塩酸、臭化水素酸
、ヨウ化水素酸、硝酸または硫酸などの鉱酸との塩が挙
げられる。
Salts of 3-aminopyrrolidine include salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid or sulfuric acid.

また、本発明方法の原料である一般式CI)の化合物は
、たとえば、米国特許第3365450号公報などく記
載された方法で、下記の製造ルートに従って製造するこ
とができる。
Further, the compound of general formula CI), which is a raw material for the method of the present invention, can be produced, for example, by the method described in US Pat. No. 3,365,450, according to the following production route.

〔■〕[■]

つぎに、実施例を挙げて本発明を説明するが、本発明は
、これに限定されるものではない。
Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto.

実施例 (1)1−エトキシカルボニル−3−ピロリドン100
?をメタノール300−に溶解させ、水素化ホウ素ナト
リウム6.02fを水401ntに溶解させた溶液を、
0℃で30分を要して滴下する。さらに同温度で15分
反応させた後、製塩5214.3d、飽和食壌水250
PILtおよび塩化メチレン300dを順次加える。つ
いで、有機層を分取し、飽和食塩水100コで洗浄し、
無水硫酸マグネシウムで乾燥させた後、減圧下に溶媒を
留去すれは、油状の1−エトキシカルボニル−3−ヒド
ロキシピロリジン100?(収率98.7 % )を得
る。
Example (1) 1-ethoxycarbonyl-3-pyrrolidone 100
? was dissolved in 300 ml of methanol, and 6.02 f of sodium borohydride was dissolved in 401 nt of water.
Add dropwise at 0°C over 30 minutes. After further reacting at the same temperature for 15 minutes, 5214.3 d of salt and 250 d of saturated loam water were added.
PILt and 300 d of methylene chloride are added sequentially. Next, the organic layer was separated and washed with 100 liters of saturated saline solution.
After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain oily 1-ethoxycarbonyl-3-hydroxypyrrolidine. (yield 98.7%).

IR(ニー) ) cm−” i νc=o  167
ONMR(CDCIs)δ値; 1.30(3H,t 、 J=7Hz 、CH,CH,
−) 。
IR (knee) cm-” i νc=o 167
ONMR (CDCIs) δ value; 1.30 (3H, t, J=7Hz, CH, CH,
−).

4.15 (2H、q 、 J=7Hz 、 CH3C
H2−) 。
4.15 (2H, q, J=7Hz, CH3C
H2-).

(2+  1−エトキシカルボニル−3−ヒト0ロキシ
ビロリジン100tを塩化メチレン500dに溶解させ
、トリエチルアミン63.5tを加えた後、メシルクロ
リド72.(lを0℃で1時間を要して滴下する。さら
に同温度で20分反志させた後、水500dを加える。
(2+ 100 t of 1-ethoxycarbonyl-3-human 0-roxyvirolidine is dissolved in 500 d of methylene chloride, 63.5 t of triethylamine is added, and then 72 liters of mesyl chloride is added dropwise at 0°C over 1 hour. After stirring at the same temperature for 20 minutes, add 500 d of water.

ついで、有機層を分取し、飽和食塩水200111tで
洗浄し、無水硫酸マグネシウムで乾燥させた後、減圧下
に溶媒を留去すれば、油状の1−エトキシカルボニル−
3−メシルオキシピロリジン128t(収率85.9%
)を得る。
Then, the organic layer was separated, washed with 200111t of saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain oily 1-ethoxycarbonyl-
128t of 3-mesyloxypyrrolidine (yield 85.9%)
).

IRに−ト) ctn−1i  シ、=0168ONM
R(CDCI、 )δ値; 1.28 (3H、L 、 J=7Hz 、 CHIC
H,−) 。
to IR) ctn-1i =0168ONM
R (CDCI, ) δ value; 1.28 (3H, L, J=7Hz, CHIC
H, -).

3.08(3u、 a 、−oso2cm)。3.08 (3u, a, -oso2cm).

4.16 (2H,q 、 J=7Hz 、 CH3C
H2−) 。
4.16 (2H,q, J=7Hz, CH3C
H2-).

(3)  1−エトキシカルボニル−3−メシルオキシ
ピロリジン100t f N、N−ジメチルホルムアミ
ド750dに溶解させ、N−カリウムフタルイミド78
fを加えて、100℃で2時間反応させる。
(3) 100 t f of 1-ethoxycarbonyl-3-mesyloxypyrrolidine dissolved in 750 d of N,N-dimethylformamide, and 78 t of N-potassium phthalimide.
Add f and react at 100°C for 2 hours.

ついで、室温まで冷却した後、塩化メチレン500−お
よび水2250ajを加え、20憾水酸化ナトリウム水
溶液でpH11,5に調整する。有機層を分取し、0.
IN−塩酸500−1水500Int  および飽和食
塩水250−で順次洗浄し、無水硫酸マグネシウムで乾
燥させた後、減圧下に溶媒を留去する。得られた残留物
にジイソプロピルエーテル200#Egを加えて、析出
した結晶性物質をF取すれば、融点81〜82℃を示す
1−エトキシカルボニル−3−フタルイミドピロリジン
52.0?(収率42.8係)を得る。
After cooling to room temperature, 500 ml of methylene chloride and 2250 ml of water were added, and the pH was adjusted to 11.5 with 20 ml of aqueous sodium hydroxide solution. The organic layer was separated and 0.
After sequentially washing with 500 Int of IN-hydrochloric acid, 500 Int of water and 250 Int of saturated brine, and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. Diisopropyl ether 200#Eg was added to the obtained residue, and the precipitated crystalline substance was collected by F. 1-ethoxycarbonyl-3-phthalimidopyrrolidine having a melting point of 81 to 82°C was obtained at 52.0°C. (yield: 42.8%).

IR(KBr ) ctn(;νc=o  170ON
MR(cnc13)δ値; 1.28(3H,t、J=7Hz、CH,CH2−)。
IR(KBr) ctn(;νc=o 170ON
MR (cnc13) δ value; 1.28 (3H, t, J=7Hz, CH, CH2-).

−〇 4.10 (2H、q 、 J=7Hz 、CH2CH
2−) 。
-〇4.10 (2H, q, J=7Hz, CH2CH
2-).

(4)l−エトキシカルボニル−3−7タルイミドピロ
リジン50.OFに製塩#500−を加え、1゜時間加
熱還流させる。ついで、反応液を室温まで冷却した後、
不溶物を戸去する。F液を減圧下に留去し、得られた結
晶性物質をエタノール25−で洗浄すれば、吸湿性の3
−アミノピロリジン・2塩酸塩24.2fC収率87.
7%)を得る。
(4) l-ethoxycarbonyl-3-7thalimidopyrrolidine 50. Add salt #500 to OF and heat to reflux for 1 hour. Then, after cooling the reaction solution to room temperature,
Remove insoluble matter. If the F solution is distilled off under reduced pressure and the obtained crystalline substance is washed with ethanol 25-, the hygroscopic 3
-Aminopyrrolidine dihydrochloride 24.2fC yield 87.
7%).

IR(ヌジョール) cIn−” i  νNH2”*
 HH,”  5000〜20’0ONMB(D*O)
 a値; (5)3−アミノピロリジン・2塩酸!15.9P、に
メタノール50−を加え、さらに、ナトリウムメチラー
)10.8Fを加える。室温で1時間攪拌した後、不溶
物を戸去し、得られたF液を蒸留すれば、沸点156℃
を示す3−アミノピロリジンを得る。
IR (Nujol) cIn-” i νNH2”*
HH,” 5000~20'0ONMB(D*O)
a value; (5) 3-aminopyrrolidine dihydrochloric acid! Add 50-methanol to 15.9P, and then add 10.8F of sodium methylate. After stirring at room temperature for 1 hour, the insoluble matter was removed and the resulting F solution was distilled to have a boiling point of 156°C.
3-aminopyrrolidine is obtained.

rg(ニー) ) cm−1:  シNu、NH,33
50〜315ONMR(CDCh)δ値;
rg (knee) cm-1: Nu, NH, 33
50-315ONMR (CDCh) δ value;

Claims (1)

【特許請求の範囲】 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示す。〕で表わされ
る化合物を鉱酸と反応させることを特徴とする3−アミ
ノピロリジンまたはその塩の製造法。
[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R^1 represents a lower alkyl group. A method for producing 3-aminopyrrolidine or a salt thereof, which comprises reacting a compound represented by the following with a mineral acid.
JP17843884A 1984-08-29 1984-08-29 Preparation of 3-aminopyrrolidine or its salt Granted JPS6157579A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP17843884A JPS6157579A (en) 1984-08-29 1984-08-29 Preparation of 3-aminopyrrolidine or its salt

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP17843884A JPS6157579A (en) 1984-08-29 1984-08-29 Preparation of 3-aminopyrrolidine or its salt

Publications (2)

Publication Number Publication Date
JPS6157579A true JPS6157579A (en) 1986-03-24
JPH0413339B2 JPH0413339B2 (en) 1992-03-09

Family

ID=16048517

Family Applications (1)

Application Number Title Priority Date Filing Date
JP17843884A Granted JPS6157579A (en) 1984-08-29 1984-08-29 Preparation of 3-aminopyrrolidine or its salt

Country Status (1)

Country Link
JP (1) JPS6157579A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5137877A (en) * 1990-05-14 1992-08-11 Bristol-Myers Squibb Bifunctional linking compounds, conjugates and methods for their production

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5137877A (en) * 1990-05-14 1992-08-11 Bristol-Myers Squibb Bifunctional linking compounds, conjugates and methods for their production
US5349066A (en) * 1990-05-14 1994-09-20 Bristol-Myers Squibb Company Bifunctional linking compounds, conjugates and methods for their production

Also Published As

Publication number Publication date
JPH0413339B2 (en) 1992-03-09

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