JP2762106B2 - Method for producing 3-hydroxypyrrolidine - Google Patents
Method for producing 3-hydroxypyrrolidineInfo
- Publication number
- JP2762106B2 JP2762106B2 JP1080389A JP8038989A JP2762106B2 JP 2762106 B2 JP2762106 B2 JP 2762106B2 JP 1080389 A JP1080389 A JP 1080389A JP 8038989 A JP8038989 A JP 8038989A JP 2762106 B2 JP2762106 B2 JP 2762106B2
- Authority
- JP
- Japan
- Prior art keywords
- hydroxypyrrolidine
- reaction
- benzyl
- present
- water
- 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 - Fee Related
Links
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
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyrrole Compounds (AREA)
Description
【発明の詳細な説明】 （産業上の利用分野） 本発明は、３−ヒドロキシピロリジンの製造方法に関
する。Description: TECHNICAL FIELD The present invention relates to a method for producing 3-hydroxypyrrolidine.
さらに詳しくは、１−ベンジル−３−ヒドロキシピロ
リジン類を、貴金属触媒を用いて水の存在下に水素化分
解させることによる、３−ヒドロキシピロリジンの製造
方法に関する。More specifically, the present invention relates to a method for producing 3-hydroxypyrrolidine by hydrogenating 1-benzyl-3-hydroxypyrrolidine in the presence of water using a noble metal catalyst.
３−ヒドロキシピロリジンは、医薬・農薬等の合成原
料として有用な化合物である。3-Hydroxypyrrolidine is a compound useful as a raw material for synthesis of medicines, agricultural chemicals and the like.
（従来技術及び発明が解決しようとする課題） 従来、３−ヒドロキシピロリジンの製造方法として
は、１−ベンジル−３−ヒドロキシピロリジンを、エタ
ノール中で酢酸塩とした後、Pd/C触媒の存在下において
水素化分解する方法（シンセティックコミュニケーショ
ンズ13（13）1117−1123（1983））等が知られている。
この方法においては目的物が酢酸塩として得られるため
に中和工程が必要である。また、中和後の反応液は無機
塩を含むため有機抽出剤での抽出操作が必要となり、３
−ヒドロキシピロリジンは有機層への分配率があまり高
くないので、その抽出単離を簡便に行ないがたい。(Prior Art and Problems to be Solved by the Invention) Conventionally, as a method for producing 3-hydroxypyrrolidine, 1-benzyl-3-hydroxypyrrolidine is converted into an acetate in ethanol, and then is reacted in the presence of a Pd / C catalyst. A method of hydrocracking (Synthetic Communications 13 (13) 111-1123 (1983)).
In this method, a neutralization step is required in order to obtain the target substance as an acetate. Further, since the reaction solution after neutralization contains an inorganic salt, an extraction operation with an organic extractant is required, and the
-Hydroxypyrrolidine does not have a very high partitioning ratio to the organic layer, so it is difficult to extract and isolate it easily.
（課題を解決するための手段） 本発明者は、検討を重ねた結果意外にも反応時に水を
存在せしめることにより酸を用いることなく１−ベンジ
ル−３ヒドロキシピロリジン類のＮ原子と、ベンジル基
のCH2の結合の開裂がすみやかに行われることを見出し
本発明を完成するに至った。(Means for Solving the Problems) As a result of repeated studies, the present inventors have surprisingly found that the presence of water during the reaction allows the N atom of the 1-benzyl-3-hydroxypyrrolidine and the benzyl group to be used without using an acid. bond cleavage of CH 2 was thus completed the present invention found that the quickly performed.
すなわち本発明は、一般式〔１〕： 〔式中、Ｘは水素原子、ハロゲン原子または炭素数/1〜
４の低級アルキル基を表す〕 で示される１−ベンジル−３−ヒドロキシピロリジン類
を水の存在下で貴金属触媒を用いて水素化分解させるこ
とを特徴とする３−ヒドロキシピロリジンの製造方法を
提供するものである。That is, the present invention provides a compound represented by the general formula [1]: [Wherein X is a hydrogen atom, a halogen atom or a carbon number / 1 to
4 represents a lower alkyl group). 1-benzyl-3-hydroxypyrrolidine represented by the formula: is hydrogenated in the presence of water using a noble metal catalyst to provide a process for producing 3-hydroxypyrrolidine. Things.
上記式〔１〕で示される１−ベンジル−３−ヒドロキ
シピロリジン類において、Ｒが炭素数１〜４の低級アル
キル基を表すときには、Ｒは例えばメチル基、プロピル
基、イソプロピル基、ブチル基、イソブチル基、sec−
ブチル基、tert−ブチル基の直鎖状または分岐状のアル
キル基である。Ｒがハロゲン原子を表す場合には、例え
ばフッ素、塩素、臭素、ヨウ素である。In the 1-benzyl-3-hydroxypyrrolidines represented by the above formula [1], when R represents a lower alkyl group having 1 to 4 carbon atoms, R is, for example, a methyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group. Group, sec-
It is a linear or branched alkyl group of a butyl group or a tert-butyl group. When R represents a halogen atom, it is, for example, fluorine, chlorine, bromine or iodine.
反応時に使用する水の量は、１−ベンジル−３−ヒド
ロキシピロリジン類に対し0.1倍〜10倍、好ましくは0.5
〜３倍である。本発明の方法は無有機溶媒下で行なうの
が好ましいが、有機溶媒を共存させて行なうこともでき
る。The amount of water used in the reaction is 0.1 to 10 times, preferably 0.5 to 1-benzyl-3-hydroxypyrrolidine.
~ 3 times. The method of the present invention is preferably performed in the absence of an organic solvent, but may be performed in the presence of an organic solvent.
有機溶媒としては、メタノール、エタノール、プロパ
ノール等のアルコール類；ベンゼン、トルエン、シクロ
ヘキサン等の炭化水素類；ジエチルエーテル、テトラハ
イドロフラン、ジオキサン等のエーテル類；あるいは塩
化メチレン、ジメチルホルムアミド等をあげることがで
きる。これらの中でもアルコール類を使用するのが好ま
しい。Examples of the organic solvent include alcohols such as methanol, ethanol, and propanol; hydrocarbons such as benzene, toluene, and cyclohexane; ethers such as diethyl ether, tetrahydrofuran, and dioxane; and methylene chloride and dimethylformamide. it can. Among them, it is preferable to use alcohols.
また、本反応においては、水素化分解触媒としてラネ
ー触媒を用いると目的物の収率は極めて低いものである
が、貴金属触媒を使用するとラネー触媒に比べて格段に
優れた収率で目的物を得ることができる。したがって、
本発明においては貴金属触媒を用いることが重要であ
る。貴金属触媒としては、好ましくは、白金族元素、例
えばPd,Pt,Rh,Ru等を使用する。これらは単独で、ある
いは活性炭等に担持された形で使用してもよい。使用す
る量は、１−ベンジル−３−ヒドロキシピロリジン類に
対し、0.001重量％〜20重量％，好ましくは0.1重量％〜
５重量％である。本反応における水素圧は常圧〜150Kgc
m-2，好ましくは５〜60Kgcm-2である。In addition, in this reaction, the yield of the target product is extremely low when a Raney catalyst is used as the hydrocracking catalyst, but the use of the noble metal catalyst allows the target product to be obtained at a much higher yield than the Raney catalyst. Obtainable. Therefore,
In the present invention, it is important to use a noble metal catalyst. As the noble metal catalyst, a platinum group element such as Pd, Pt, Rh, Ru or the like is preferably used. These may be used alone or in a form supported on activated carbon or the like. The amount to be used is 0.001% by weight to 20% by weight, preferably 0.1% by weight to 1-benzyl-3-hydroxypyrrolidine.
5% by weight. Hydrogen pressure in this reaction is from normal pressure to 150 Kgc
m −2 , preferably 5 to 60 Kgcm −2 .
次に、反応温度は０〜150℃，好ましくは20〜100℃で
あり、反応時間は反応温度、水の添加量、触媒量等によ
り適宜選択することができるが通常１〜４時間である。Next, the reaction temperature is 0 to 150 ° C., preferably 20 to 100 ° C., and the reaction time can be appropriately selected depending on the reaction temperature, the amount of water added, the amount of catalyst, and the like, but is usually 1 to 4 hours.
本発明において生成した３−ヒドロキシピロリジンの
単離精製は、反応終了後、触媒の濾別、水ないし溶媒等
の留去、および蒸留により容易に行うことができる。本
発明方法においては、このようにして高純度の３−ヒド
ロキシピロリジンが高収率で得られる。After the completion of the reaction, the isolation and purification of the 3-hydroxypyrrolidine produced in the present invention can be easily carried out by filtration of the catalyst, evaporation of water or a solvent, and distillation. In the method of the present invention, 3-hydroxypyrrolidine with high purity is thus obtained in high yield.
なお、本発明において原料として用いられる１−ベン
ジル−３−ヒドロキシピロリジン類は、１−ベンジル−
３−ピロリジノン類を還元することにより得ることがで
きる。In the present invention, 1-benzyl-3-hydroxypyrrolidine used as a raw material is 1-benzyl-
It can be obtained by reducing 3-pyrrolidinones.
以下に実施例を示し、さらに詳細に本発明を説明する
が、本発明はそれらの実施例に限定されるものではな
い。Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
実施例１ 容量１の電磁式撹拌式オートクレーブに、１−ベン
ジル−３−ヒドロキシピロリジン177g（1.0モル）,5％
パラジウム−カーボン8.9gを仕込みさらに水177gを加え
た後、水素を導入及び加熱して100℃,40気圧に昇温昇圧
し２時間反応させた。水素吸収は水素導入開始後１時間
で終了した。反応終了後、オートクレーブを室温まで冷
却して放圧した。反応液を取り出し、触媒を濾別した
後、トルエン共沸脱水により水を留去、およびトルエン
を留去し，残液を蒸留して３−ヒドロキシピロリジン8
1.2g（収率93.3％）を得た。この留分をガスクロマトグ
ラフィーにより分析したところ99.7％の純度であった。Example 1 177 g (1.0 mol) of 1-benzyl-3-hydroxypyrrolidine, 5%
After charging 8.9 g of palladium-carbon and further adding 177 g of water, hydrogen was introduced and heated to 100 ° C., the pressure was raised to 40 atm, and the reaction was carried out for 2 hours. Hydrogen absorption was completed one hour after the start of hydrogen introduction. After the reaction was completed, the autoclave was cooled to room temperature and depressurized. After the reaction solution was taken out and the catalyst was filtered off, water was distilled off by azeotropic dehydration with toluene, and toluene was distilled off.
1.2 g (93.3% yield) was obtained. This fraction was analyzed by gas chromatography and found to be 99.7% pure.
沸点:109〜112℃/12mmHg 実施例２ 反応温度を80℃に代えた他は実施例１と同様にして反
応及び後処理を行い、純度99.7％の３−ヒドロキシピロ
リジンを79.2g（収率91.0％）得た。Boiling point: 109-112 ° C / 12mmHg Example 2 The reaction and post-treatment were carried out in the same manner as in Example 1 except that the reaction temperature was changed to 80 ° C, and 79.2 g of 3-hydroxypyrrolidine having a purity of 99.7% was obtained (yield 91.0%). %)Obtained.
実施例３ 溶媒としてメタノール89gを使用し、水の量を89gとし
た他は実施例１と同様に反応及び後処理を行い、純度9
9.8％の３−ヒドロキシピロリジンを147.6g（収率83.3
％）で得た。Example 3 A reaction and a post-treatment were carried out in the same manner as in Example 1 except that 89 g of methanol was used as a solvent and the amount of water was 89 g.
147.6 g of 9.8% 3-hydroxypyrrolidine (83.3% yield)
%).
実施例４ 溶媒をキシレン89gとした他は実施例３と同様に反応
及び後処理を行い、純度99.6％の３−ヒドロキシピロリ
ジンを143.0g（収率80.7％）得た。Example 4 The reaction and post-treatment were carried out in the same manner as in Example 3 except that 89 g of xylene was used as the solvent, to obtain 143.0 g (yield: 80.7%) of 3-hydroxypyrrolidine having a purity of 99.6%.
本発明によれば、医薬、農薬等の原体・中間体の合成
原料として有用な３−ヒドロキシピロリジンを従来方法
のごとき煩雑な後処理をすることなく容易に、高純度か
つ収率良く製造することができる。According to the present invention, 3-hydroxypyrrolidine useful as a raw material for synthesizing a drug substance, an agrochemical or the like as a raw material / intermediate can be easily produced with high purity and high yield without complicated post-treatment as in a conventional method. be able to.
Claims (1)
４の低級アルキル基を表す〕 で示される１−ベンジル−３−ヒドロキシピロリジン類
を水の存在下に貴金属触媒を用いて水素化分解させるこ
とを特徴とする３−ヒドロキシピロリジンの製造方法。1. The general formula [1]: [Wherein X is a hydrogen atom, a halogen atom or a carbon number of 1 to
A lower alkyl group of 4) is hydrogenated using a noble metal catalyst in the presence of water to produce 3-hydroxypyrrolidine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1080389A JP2762106B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 3-hydroxypyrrolidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1080389A JP2762106B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 3-hydroxypyrrolidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02258762A JPH02258762A (en) | 1990-10-19 |
| JP2762106B2 true JP2762106B2 (en) | 1998-06-04 |
Family
ID=13716933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1080389A Expired - Fee Related JP2762106B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 3-hydroxypyrrolidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2762106B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004244418A (en) * | 2003-01-21 | 2004-09-02 | Toray Fine Chemicals Co Ltd | Method for production of n-methyl nitrogen-containing cyclic alcohol |
-
1989
- 1989-03-30 JP JP1080389A patent/JP2762106B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02258762A (en) | 1990-10-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2079486C1 (en) | Method for synthesis of formoterol or its derivatives | |
| EP0441160A1 (en) | Process for preparing levo and dextro fenfluramine | |
| KR960000758B1 (en) | Optically active hydroxybenzylamine derivative, optically active | |
| JP2762106B2 (en) | Method for producing 3-hydroxypyrrolidine | |
| JPH0359051B2 (en) | ||
| JP3205648B2 (en) | Method for producing 2-chloro-5-aminomethylpyridine | |
| JPH0246590B2 (en) | ||
| JP2915161B2 (en) | Process for producing optically active amino alcohols and intermediates thereof | |
| US4231962A (en) | 3-Phenoxybenzylideneamines and 3-benzylbenzylideneamines | |
| US5777170A (en) | Process for the preparation of a naphthylbutanone | |
| US4910343A (en) | Nitroamines | |
| JP4057088B2 (en) | Method for producing pyrrolidine derivative | |
| JPH02290851A (en) | Production of 2-chloru-5-aminomethylpyridine | |
| HU186528B (en) | Process for producing tetronnoic acid | |
| JPH0250101B2 (en) | ||
| EP0286991B1 (en) | Process for preparing fluorine-substituted alicyclic diols | |
| JPH05339236A (en) | Production of 2,3-diaminopyridines | |
| JPH08109170A (en) | Production of hexahydropyridazine | |
| JP4386976B2 (en) | Method for producing diketones | |
| JP2736916B2 (en) | Manufacturing method of cibeton | |
| JPH08277256A (en) | Optically active (s)-2-benzyloxycarbonylamino-1-(4-methoxyphenyl)ethanol and its production | |
| JP2512958B2 (en) | 1-biphenylylethanol derivative and process for producing the same | |
| JP3598421B2 (en) | Method for producing 2-substituted-1,3-propanediol | |
| JPH04368377A (en) | 4-amino-3-hydroxyphthalide and method for manufacturing same | |
| US4496762A (en) | Process for the preparation of N-(2-(cyclo-hexen-1-yl)ethyl)-4-methoxybenzeneacetamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |