JPH03204854A - Production of 3-amino-1-benzylpyrrolidines - Google Patents
Production of 3-amino-1-benzylpyrrolidinesInfo
- Publication number
- JPH03204854A JPH03204854A JP27372690A JP27372690A JPH03204854A JP H03204854 A JPH03204854 A JP H03204854A JP 27372690 A JP27372690 A JP 27372690A JP 27372690 A JP27372690 A JP 27372690A JP H03204854 A JPH03204854 A JP H03204854A
- Authority
- JP
- Japan
- Prior art keywords
- benzyl
- hydrogen
- ammonia
- raw material
- amino
- 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
Links
- HBVNLKQGRZPGRP-UHFFFAOYSA-N 1-benzylpyrrolidin-3-amine Chemical class C1C(N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-UHFFFAOYSA-N 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- DHGMDHQNUNRMIN-UHFFFAOYSA-N 1-benzylpyrrolidin-3-one Chemical class C1C(=O)CCN1CC1=CC=CC=C1 DHGMDHQNUNRMIN-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 19
- 239000002994 raw material Substances 0.000 abstract description 13
- 239000007868 Raney catalyst Substances 0.000 abstract description 9
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 abstract description 9
- 229910000564 Raney nickel Inorganic materials 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000010531 catalytic reduction reaction Methods 0.000 abstract description 6
- 239000003905 agrochemical Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000010941 cobalt Substances 0.000 abstract description 2
- 229910017052 cobalt Inorganic materials 0.000 abstract description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 1
- 239000003863 metallic catalyst Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 15
- YQMXOIAIYXXXEE-UHFFFAOYSA-N 1-benzylpyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- -1 1,2,4-trisubstituted-butanes Chemical class 0.000 description 2
- CWEGCQIIDCZZED-UHFFFAOYSA-N 1-benzylpyrrolidine Chemical class C=1C=CC=CC=1CN1CCCC1 CWEGCQIIDCZZED-UHFFFAOYSA-N 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- SFEGZLNDKUGHQJ-UHFFFAOYSA-N 1-benzyl-2-methylpyrrolidin-3-amine Chemical compound CC1C(N)CCN1CC1=CC=CC=C1 SFEGZLNDKUGHQJ-UHFFFAOYSA-N 0.000 description 1
- KQGNDKNHORROII-UHFFFAOYSA-N 1-benzyl-2-methylpyrrolidin-3-one Chemical compound C1CC(=O)C(C)N1CC1=CC=CC=C1 KQGNDKNHORROII-UHFFFAOYSA-N 0.000 description 1
- MKRBAPNEJMFMHU-UHFFFAOYSA-N 1-benzylpyrrole-2,5-dione Chemical class O=C1C=CC(=O)N1CC1=CC=CC=C1 MKRBAPNEJMFMHU-UHFFFAOYSA-N 0.000 description 1
- FZDRDGCVSLQCQB-UHFFFAOYSA-N 1-benzylpyrrolidin-2-ol Chemical compound OC1CCCN1CC1=CC=CC=C1 FZDRDGCVSLQCQB-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- NJPNCMOUEXEGBL-UHFFFAOYSA-N pyrrolidin-1-ium-3-ylazanium;dichloride Chemical compound Cl.Cl.NC1CCNC1 NJPNCMOUEXEGBL-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical class NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Catalysts (AREA)
Abstract
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−１−ベンジルピロリジン類の製
造法に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for producing 3-amino-1-benzylpyrrolidines.
従来技術
３−アミノ−１−ベンジルピロリジン類は、医薬、農薬
合成用中間体として多様な用途が期待される有用な化合
物である。BACKGROUND OF THE INVENTION 3-Amino-1-benzylpyrrolidines are useful compounds that are expected to have a variety of uses as intermediates for the synthesis of pharmaceuticals and agricultural chemicals.
従来、３−アミノ−１−ベンジルピロリジン類の製造法
としては、■１，２．４−トリ置換−ブタン類（置換基
は、ハロゲン又はアルキルスルホニル基を示す）にベン
ジルアミンを反応させ、次いでアンモニアを反応させる
方法（特開昭６３−４１４５２号公報）、■１−ベンジ
ルー３−ピロリンー２，５−ジオン類をアンモニアと反
応させた後カルボニル基を還元する方法（特開平１−１
０６８６２号公報）、■１−ベンジル−３−ピコリジノ
ンオキシム類を還元する方法（特開昭５３−２８１６１
号公報）、■１−ベンジルー３＝フタルイミドピロリジ
ン類とヒドラジンを反応させる方法（Ｊ、 Ｍｅｄ、Ｃ
ｈｅｍ、、 Ｖｏｌ、 １１゜１０３４ （１９６８
）等が知られている。Conventionally, as a method for producing 3-amino-1-benzylpyrrolidines, 1,2,4-trisubstituted-butanes (the substituent represents a halogen or an alkylsulfonyl group) are reacted with benzylamine, and then A method of reacting with ammonia (Japanese Unexamined Patent Application Publication No. 1983-41452), ■ A method of reacting 1-benzyl-3-pyrroline-2,5-diones with ammonia and then reducing the carbonyl group (Japanese Unexamined Patent Publication No. 1-1999)
06862), ■ Method for reducing 1-benzyl-3-picolidinone oximes (Japanese Patent Application Laid-Open No. 53-28161)
1-benzy-3-phthalimidopyrrolidine and hydrazine (J, Med, C
hem,, Vol, 11゜1034 (1968
) etc. are known.
発明が解決しようとする問題点
しかしながら、上記従来の製造法のうち■の方法及び■
の方法では、工程が長い上に低収率（■の方法では３３
％、■の方法では３１．１％）であり、■の方法では、
使用原料であるオキシムが不安定であり、また■の方法
では使用原料であるヒドラジンが有害であり、工業的に
製造するには危険を伴う。従って上記■〜■のいずれの
場合も工業的製造法として充分なものとは言い難い。Problems to be Solved by the Invention However, among the above conventional manufacturing methods, method (■) and method (■)
In method (■), the process is long and the yield is low (method (■) is 33%
%, 31.1% in method ■), and in method ■,
The oxime used as a raw material is unstable, and the hydrazine used in method (2) is harmful, making it dangerous to produce industrially. Therefore, it is difficult to say that any of the above cases (1) to (2) are sufficient as industrial production methods.
本発明の目的はかかる欠点を克服し、工業的に有利な３
−アミノ−１−ベンジルピロリジン類の製造法を提供す
ることにある。The object of the present invention is to overcome such drawbacks and to provide three industrially advantageous
An object of the present invention is to provide a method for producing -amino-1-benzylpyrrolidines.
問題点を解決するための手段
本発明者らは１−ベンジル−３−ピロリジノン類のアミ
ノ化について研究を重ねた結果、アンモニア及び還元触
媒の存在下に１−ベンジル−３−ピロリジノン類を水素
によって接触還元することにより３−アミノ−１−ベン
ジルピロリジン類を一工程でしかも高収率で製造する方
法を見出し本発明を完成した。Means for Solving the Problems As a result of repeated research on the amination of 1-benzyl-3-pyrrolidinones, the present inventors found that 1-benzyl-3-pyrrolidinones were oxidized by hydrogen in the presence of ammonia and a reduction catalyst. The present invention was accomplished by discovering a method for producing 3-amino-1-benzylpyrrolidines in one step and in high yield by catalytic reduction.
即ち本発明によれば、式（１）：
［式中、Ｒは水素原子又は低級アルキル基を示す。］
で示される１−ベンジル−３−ピロリジノン類をアンモ
ニア及び還元触媒の存在下に水素によって還元するだけ
で簡単に且っ高収率で式（２）：［式中、Ｒは前記に同
じ。］
で示される３−アミノ−１−ベンジルピロリジンを得る
ことができる。That is, according to the present invention, formula (1): [wherein R represents a hydrogen atom or a lower alkyl group]. ] 1-Benzyl-3-pyrrolidinones represented by formula (2): [wherein R is the same as above] can be easily and in high yield simply by reducing with hydrogen in the presence of ammonia and a reduction catalyst. ] 3-Amino-1-benzylpyrrolidine can be obtained.
本明細書において、Ｒで示される低級アルキル基として
は、例えばメチル基、エチル基、ｎ−プロピル基、イソ
プロピル基、ｎ−ブチル基、１ｅｒｌ−ブチル基等が挙
げられる。In this specification, examples of the lower alkyl group represented by R include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, and erl-butyl group.
以下、本発明の具体的な方法について説明する。Hereinafter, a specific method of the present invention will be explained.
本発明で使用する還元触媒は接触還元に使用される一般
的な金属触媒でよく、例えばラネーニッケル、ラネーコ
バルト、パラジウムカーボン、白金カーボン等が挙げら
れ、通常これらの触媒を原料化合物に対して０．５〜１
００＋ｒｆ％、好ましくは１〜２０ｗｆ％用いるのがよ
い。The reduction catalyst used in the present invention may be a general metal catalyst used in catalytic reduction, such as Raney nickel, Raney cobalt, palladium carbon, platinum carbon, etc. These catalysts are usually used at a ratio of 0.0% to the raw material compound. 5-1
It is preferable to use 00+rf%, preferably 1 to 20wf%.
■−ベンジルー３−ピロリジノンのアミノ化反応は、通
常オートクレーブ中でキシレン、トルエン、メタノール
、エタノール、水等の単一或は混合溶媒系中で行なうこ
とができる。(1) The amination reaction of benzyl-3-pyrrolidinone can be carried out usually in an autoclave in a single or mixed solvent system such as xylene, toluene, methanol, ethanol, water and the like.
アンモニアは原料化合物に対して、通常１〜５０倍モル
、好ましくは１．０〜２０倍モル使用し、接触還元に用
いる水素は、通常反応開始前にオートクレーブ中に加え
られる。しかし、原料化合物として１−ベンジル−３−
ピロリジノンを使用する場合、反応開始前に水素を加え
る方法では副生物である１−ベンジル−３−ヒドロキシ
ピロリジンが増加し、目的物の収率が低下するため、昇
温し所定の温度に到達してから水素を加える方法を採用
するのが好ましい。Ammonia is usually used in a molar amount of 1 to 50 times, preferably 1.0 to 20 times, based on the raw material compound, and hydrogen used for catalytic reduction is usually added to the autoclave before the start of the reaction. However, as a raw material compound, 1-benzyl-3-
When using pyrrolidinone, adding hydrogen before the start of the reaction increases the by-product 1-benzyl-3-hydroxypyrrolidine and reduces the yield of the target product, so the temperature must be raised to reach the specified temperature. It is preferable to adopt a method in which hydrogen is added after the addition of hydrogen.
反応温度としては、通常室温から２００℃の範囲内で適
宜選択すればよいが、好ましくは９０°Ｃ以上が好適で
ある。また、反応圧としては、通常は常圧以上、好まし
くは５〜４０）ｃｇ／ｃｉである。The reaction temperature may be selected as appropriate within the range of usually room temperature to 200°C, but preferably 90°C or higher. The reaction pressure is usually at least normal pressure, preferably from 5 to 40) cg/ci.
反応時間は、通常３０分〜３時間で完結する。また原料
の１−ベンジル−３−ピロリジノン類は、昇温後オート
クレーブ中に圧入することにより反応させてもよい。The reaction time is usually 30 minutes to 3 hours. Further, the raw material 1-benzyl-3-pyrrolidinone may be reacted by being pressurized into an autoclave after raising the temperature.
反応後、触媒を炉別し、が液を蒸留することにより目的
物が得られる。After the reaction, the catalyst is separated from the furnace and the liquid is distilled to obtain the desired product.
発明の効果
従来の３−アミノ−１−ベンジルピロリジン類の製造法
は、工程数が長いか、使用原料が危険物である等の理由
により、工業的製法としては数々の問題があった。これ
に対して、１−ベンジル３−ピロリジノン類の３位のカ
ルボニルとアンモニアとの脱水反応、及び水素による接
触還元を同一反応系内で行なう本発明の製造法は入手の
容易な原料を用い一工程でしかも高収率で３−アミノ１
−ベンジルピロリジン類を得ることができる工業的に有
利な方法である。Effects of the Invention Conventional methods for producing 3-amino-1-benzylpyrrolidines have had a number of problems as an industrial production method due to the long number of steps and the use of dangerous raw materials. In contrast, the production method of the present invention, in which the dehydration reaction of the carbonyl at the 3-position of 1-benzyl-3-pyrrolidinones with ammonia and the catalytic reduction with hydrogen are carried out in the same reaction system, uses easily available raw materials. 3-amino 1 in a process with high yield
-This is an industrially advantageous method for obtaining benzylpyrrolidines.
尚、３−アミノ−１−ベンジルピロリジン類は、その構
造から予想される様に、医薬・農薬等の生理活性物質の
合成原料として用いられる。例えば、３−アミノ−１−
ベンジルピロリジン・２塩酸塩をパラジウムカーボン存
在下で接触還元すると脱ベンジル化して、高収率で３−
アミノピロリジン・２塩酸塩が得られるが、この３−ア
ミノピロリジンは、医薬・農薬の合成原料として有用で
ある。As expected from its structure, 3-amino-1-benzylpyrrolidines are used as raw materials for the synthesis of physiologically active substances such as medicines and agricultural chemicals. For example, 3-amino-1-
When benzylpyrrolidine dihydrochloride is catalytically reduced in the presence of palladium carbon, it is debenzylated and 3-
Aminopyrrolidine dihydrochloride is obtained, and this 3-aminopyrrolidine is useful as a raw material for the synthesis of pharmaceuticals and agricultural chemicals.
実施例
以下に実施例を示して本発明を説明するが、本発明はこ
れらの実施例に限定されるものではない。EXAMPLES The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples.
実施例１
１−ベンジル−３−ピロリジノン１３１ｇ１キシレン２
６２ ｇ、メタノール７５ｇ１ラネーニツケル２６ｇ及
びアンモニア１９ｇをオートクレーブ中に加え、温度１
２０℃で水素を加え内圧４０ｋｇ／ｃｉで１時間３０分
撹拌した。反応中に消費される水素を供給しながら内圧
を４０ｋｇ／ｃａｒに維持した。触媒を決別し、炉液を
濃縮した後蒸留して、沸点１３３〜１３５℃／１０ｍｍ
Ｈｇの３−アミノ−１−−ベンジルピロリジン１１７ｇ
（ＧＣ％：９８．５％、３−ヒドロキシ−１−ベンジル
ピロリジン１．４％含有）を得た。（収率：８７．３％
）
ＮＭＲ（ＣＤＣ／３）：δｐｐｍ
７、４２ （ｓ、 ５ｔｌ）、３．５５ （ｓ、 ２Ｈ
）、３．２５〜３．７２ （ｍ、 ＩＨ）１、９５〜２
．９０ （ｍ、 ６Ｈ）、］、 ３０ （ｓ、 ２Ｈ）
ＩＲ（ＫＢｒ）
３３５０．３２５０，２７７０，１６００１４９０．１
４５０．８８０ｃｍ”
実施例２
■−ベンジルー３−ピロリジノン１３１ ｇ、キシレン
２６２ ｇ、ラネーニッケル２６ｇ及びアンモニア１９
ｇをオートクレーブ中に加え、温度１２０℃で水素を加
え内圧４０ｋｇ／ａｄで１時間撹拌した。反応中に消費
される水素を供給しながら内圧を４０ｋｇ／ｃａｒに維
持した。反応液を実施例１と同様に処理して、３−アミ
ノ−１−ベンジルピロリジンｌｌ１ｇ（ＧＣ％：９６．
９％、３−ヒドロキシ−１−ベンジルピロリジン３．１
％含有）を得た。（収率：８Ｌ５％）
実施例３
ラネーニッケルの使用量を１３ｇとする以外は全て実施
例１と同様に処理して、３−アミノ−１−ペンジルピロ
リジン１１７ｇ（ＧＣ％：９８．８％、３−ヒドロキシ
−１−ベンジルピロリジン１．１％含有）を得た。（収
率：８７．５％）
実施例４
１−ベンジル−３〜ピロリジノン１３１ ｇ、メタノー
ル２６２ ｇ、ラネーニッケル２６ｇ及びアンモニア１
２７ｇをオートクレーブ中に加え、温度１２０℃水素圧
４０ｋｇ／ｃＩ［ｒで４時間撹拌した。Example 1 1-benzyl-3-pyrrolidinone 131 g 1 xylene 2
62 g of methanol, 75 g of methanol, 26 g of Raney nickel, and 19 g of ammonia were added to the autoclave, and the temperature was 1.
Hydrogen was added at 20°C, and the mixture was stirred for 1 hour and 30 minutes at an internal pressure of 40 kg/ci. The internal pressure was maintained at 40 kg/car while supplying hydrogen consumed during the reaction. After separating the catalyst and concentrating the furnace liquid, distillation is performed to obtain a boiling point of 133-135℃/10mm.
Hg of 3-amino-1-benzylpyrrolidine 117g
(GC%: 98.5%, containing 1.4% of 3-hydroxy-1-benzylpyrrolidine) was obtained. (Yield: 87.3%
) NMR (CDC/3): δppm 7, 42 (s, 5tl), 3.55 (s, 2H
), 3.25-3.72 (m, IH) 1, 95-2
．． 90 (m, 6H), ], 30 (s, 2H)
IR(KBr) 3350.3250,2770,16001490.1
450.880 cm” Example 2 - 131 g of benzyl-3-pyrrolidinone, 262 g of xylene, 26 g of Raney nickel, and 19 g of ammonia
g was added into an autoclave, hydrogen was added at a temperature of 120°C, and the mixture was stirred at an internal pressure of 40 kg/ad for 1 hour. The internal pressure was maintained at 40 kg/car while supplying hydrogen consumed during the reaction. The reaction solution was treated in the same manner as in Example 1 to obtain 1/1 g of 3-amino-1-benzylpyrrolidine (GC%: 96.
9%, 3-hydroxy-1-benzylpyrrolidine 3.1
% content) was obtained. (Yield: 8L5%) Example 3 The same procedure as in Example 1 was carried out except that the amount of Raney nickel used was changed to 13g, and 117g of 3-amino-1-penzylpyrrolidine (GC%: 98.8%, (containing 1.1% of 3-hydroxy-1-benzylpyrrolidine) was obtained. (Yield: 87.5%) Example 4 1-benzyl-3-pyrrolidinone 131 g, methanol 262 g, Raney nickel 26 g and ammonia 1
27 g was added into an autoclave and stirred for 4 hours at a temperature of 120° C. and a hydrogen pressure of 40 kg/cI [r].
反応中に消費される水素を供給しながら内圧を４０ｋｇ
／ｄに維持した。反応液を実施例１と同様に処理して３
−アミノ−１−ペンジルピロリジン１３３ｇ（ＧＣ％：
６１．４％、３−ヒドロキシ−１−ベンジルピロリジン
２８．０％含有）を得た。（収率二６１．９％）
実施例５
触媒をラネーニッケルから５％Ｐｄ−カーボンに変え５
％Ｐｄ−カーボンを３．３ｇ使用する以外は全て実施例
１と同様に処理して、３−アミノ−１−ベンジルピロリ
ジン８６ｇ（ＧＣ％：９６．２％、３−ヒドロキシ−１
−ベンジルピロリジン３．８％含有）を得た。（収率：
６２，７％）
実施例６
１−ベンジル−３−ピロリジノン１３１ ｇ、キシレン
２６２ ｇ、メタノール７５ｇ１ラネーニツケル２６ｇ
及びアンモニア１９ｇをオートクレーブ中に投入し、水
素で内圧を４０ｋｇ／Ｃｉにした。The internal pressure was increased to 40 kg while supplying the hydrogen consumed during the reaction.
/d. The reaction solution was treated in the same manner as in Example 1.
-Amino-1-penzylpyrrolidine 133g (GC%:
61.4%, containing 28.0% of 3-hydroxy-1-benzylpyrrolidine). (Yield: 61.9%) Example 5 The catalyst was changed from Raney nickel to 5% Pd-carbon.
86 g of 3-amino-1-benzylpyrrolidine (GC%: 96.2%, 3-hydroxy-1
-containing 3.8% of benzylpyrrolidine) was obtained. (yield:
62.7%) Example 6 1-benzyl-3-pyrrolidinone 131 g, xylene 262 g, methanol 75 g 1 Raney nickel 26 g
and 19 g of ammonia were put into the autoclave, and the internal pressure was adjusted to 40 kg/Ci with hydrogen.
その後１２０℃に昇温し、１．５時間撹拌した。Thereafter, the temperature was raised to 120°C and stirred for 1.5 hours.
反応中に消費される水素を供給しながら内圧を４０ｋｇ
／ａｌに維持した。反応液を実施例１と同様に処理して
３−アミノ−１−ベンジルピロリジン１３０ｇ（ＧＣ％
ニア０．７％、３−ヒドロキシ−１−ベンジルピロリジ
ン２７，８％含有）を得た。（収率：６９．７％）
実施例７
１−ベンジル−２−メチル−３−ピロリジノン９４．５
ｇ、キシレン３１５ ｇ、メタノール５０ｇ１ラネーニ
ツケル１８．９ｇ及びアンモニア１２．８ｇをオートク
レーブ中に投入し、水素で内圧を２０ｋｇ／ｃｕｔにし
た。その後１４０℃に昇温し、３時間撹拌した。反応中
に消費される水素を供給しながら内圧を２０ｋｇ／ｃａ
ｒに維持した。反応終了後、触媒を炉別し、炉液を濃縮
した後蒸留して、１−ベンジル−２−メチル−３−アミ
ノピロリジン８６．０ｇ （ＧＣ％：９８．６％、３−
ヒドロキシ−１−ベンジルピロリジン０．７％含有）を
得た。（収率：８９．３％）
ＮＭＲ（ＣＤＣ１３）： δｐｐｍ
７、２（ｓ、 ５Ｈ） 、１．７〜４．２（ｍ、 ８
ｔｌ） 、１．３８ （ｓ、 ２Ｈ）１．０〜１．３
（ｄ、ｄ、 ３８）
ＩＲ（ＫＢｒ）
３３５０．３２５０．２７７０，１６００１４９０．１
４５０ｃｍ’
（以 上）The internal pressure was increased to 40 kg while supplying the hydrogen consumed during the reaction.
/al was maintained. The reaction solution was treated in the same manner as in Example 1 to obtain 130 g of 3-amino-1-benzylpyrrolidine (GC%
27.8% of 3-hydroxy-1-benzylpyrrolidine) was obtained. (Yield: 69.7%) Example 7 1-benzyl-2-methyl-3-pyrrolidinone 94.5
g, 315 g of xylene, 50 g of methanol, 18.9 g of Raney nickel, and 12.8 g of ammonia were charged into an autoclave, and the internal pressure was adjusted to 20 kg/cut with hydrogen. Thereafter, the temperature was raised to 140°C and stirred for 3 hours. While supplying hydrogen consumed during the reaction, the internal pressure was increased to 20 kg/ca.
maintained at r. After the reaction, the catalyst was separated from the furnace, and the furnace liquid was concentrated and distilled to obtain 86.0 g of 1-benzyl-2-methyl-3-aminopyrrolidine (GC%: 98.6%, 3-
(containing 0.7% hydroxy-1-benzylpyrrolidine) was obtained. (Yield: 89.3%) NMR (CDC13): δppm 7,2 (s, 5H), 1.7-4.2 (m, 8
tl), 1.38 (s, 2H) 1.0-1.3
(d, d, 38) IR (KBr) 3350.3250.2770,16001490.1
450cm' (or more)
Claims (1)
ニア及び還元触媒の存在下に水素によって還元すること
を特徴とする式（２）： ▲数式、化学式、表等があります▼（２） ［式中、Ｒは前記に同じ。］ で示される３−アミノ−１−ベンジルピロリジン類の製
造法。[Claims] [1] Formula (1): ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (1) [In the formula, R represents a hydrogen atom or a lower alkyl group. ] Formula (2) is characterized by reducing 1-benzyl-3-pyrrolidinones represented by hydrogen with hydrogen in the presence of ammonia and a reduction catalyst: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(2) [Formula In the middle, R is the same as above. ] A method for producing 3-amino-1-benzylpyrrolidines shown below.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP27356389 | 1989-10-19 | ||
| JP1-273563 | 1989-10-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03204854A true JPH03204854A (en) | 1991-09-06 |
| JP2952702B2 JP2952702B2 (en) | 1999-09-27 |
Family
ID=17529548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP27372690A Expired - Lifetime JP2952702B2 (en) | 1989-10-19 | 1990-10-12 | Method for producing 3-amino-1-benzylpyrrolidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2952702B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114369052A (en) * | 2021-12-21 | 2022-04-19 | 赤峰万泽药业股份有限公司 | Synthetic method of 3-aminopyrrolidine dihydrochloride |
-
1990
- 1990-10-12 JP JP27372690A patent/JP2952702B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114369052A (en) * | 2021-12-21 | 2022-04-19 | 赤峰万泽药业股份有限公司 | Synthetic method of 3-aminopyrrolidine dihydrochloride |
| CN114369052B (en) * | 2021-12-21 | 2024-10-15 | 赤峰万泽药业股份有限公司 | Synthesis method of 3-aminopyrrolidine dihydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2952702B2 (en) | 1999-09-27 |
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