JPH02258763A - Production of 1-substituted-3-hydorxypyrrolidine - Google Patents
Production of 1-substituted-3-hydorxypyrrolidineInfo
- Publication number
- JPH02258763A JPH02258763A JP1080390A JP8039089A JPH02258763A JP H02258763 A JPH02258763 A JP H02258763A JP 1080390 A JP1080390 A JP 1080390A JP 8039089 A JP8039089 A JP 8039089A JP H02258763 A JPH02258763 A JP H02258763A
- Authority
- JP
- Japan
- Prior art keywords
- group
- catalyst
- substituted
- reaction
- raney
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- -1 1- substituted-3-pyrrolidinones Chemical class 0.000 claims abstract description 14
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007868 Raney catalyst Substances 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 5
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 15
- 238000011282 treatment Methods 0.000 abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 9
- 239000001257 hydrogen Substances 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 229910000564 Raney nickel Inorganic materials 0.000 abstract description 4
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 229910017052 cobalt Inorganic materials 0.000 abstract description 3
- 239000010941 cobalt Substances 0.000 abstract description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 25
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- YQMXOIAIYXXXEE-UHFFFAOYSA-N 1-benzylpyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- DHGMDHQNUNRMIN-UHFFFAOYSA-N 1-benzylpyrrolidin-3-one Chemical compound C1C(=O)CCN1CC1=CC=CC=C1 DHGMDHQNUNRMIN-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- WKBINTOKVMWIIP-UHFFFAOYSA-N 1-butylpyrrolidin-3-ol Chemical compound CCCCN1CCC(O)C1 WKBINTOKVMWIIP-UHFFFAOYSA-N 0.000 description 1
- KWFATJMDSMSKPA-UHFFFAOYSA-N 1-butylpyrrolidin-3-one Chemical compound CCCCN1CCC(=O)C1 KWFATJMDSMSKPA-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000006278 bromobenzyl group Chemical group 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 125000004803 chlorobenzyl group Chemical group 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- AQCCUQNJHACLSY-UHFFFAOYSA-N ethyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(O)C1 AQCCUQNJHACLSY-UHFFFAOYSA-N 0.000 description 1
- DQYGBMLEVQLDQC-UHFFFAOYSA-N ethyl 3-oxopyrrolidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)C1 DQYGBMLEVQLDQC-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyrrole Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は１−置換−３−ヒドロキシピロリジン類のＩＩ
造方法に関する。更に詳しくは、１−Ｗ換−３−ピロリ
ジノン類を水の存在下、水素化触媒としてラネー触媒を
用いて接触還元することによる１−１換−３−ヒドロキ
シピロリジン類の製造方法に関する。１−Ｗｔ換−３−
ヒドロキシピロリジノン類は医薬農薬等の合成原料とし
て有用な化合物である。Detailed Description of the Invention (Industrial Field of Application) The present invention relates to 1-substituted-3-hydroxypyrrolidines II
Regarding the manufacturing method. More specifically, the present invention relates to a method for producing 1-1-substituted-3-hydroxypyrrolidines by catalytically reducing 1-W-substituted-3-pyrrolidinones in the presence of water using a Raney catalyst as a hydrogenation catalyst. 1-Wt conversion-3-
Hydroxypyrrolidinones are compounds useful as synthetic raw materials for pharmaceuticals and agricultural chemicals.
（従来技術及び発明が解決しようとする問題点）従来１
−置換−３−ヒドロキシピロリジン類の製遣方法として
は１例えば１−置換−３−ピロリジノン類をリチウムア
ルミニウムハイドライド又はソヂイウムボロハイドライ
ド等の還元試薬で還元する方法等が知られている（特開
昭６３−１２２６５８）、Ｌかしながらこれらの方法で
は反応時の溶媒量が多く必要であり又後処理として中和
、抽出工程を必要とする。中和時には正確なＰＨ１１整
を行わないと蒸留の際、固化等の現象がみられ収率が低
下する。(Prior art and problems to be solved by the invention) Conventional technology 1
As a method for producing -substituted-3-hydroxypyrrolidines, for example, a method of reducing 1-substituted-3-pyrrolidinones with a reducing reagent such as lithium aluminum hydride or sodium borohydride is known ( However, these methods require a large amount of solvent during the reaction and require neutralization and extraction steps as post-treatments. If pH 11 is not adjusted accurately during neutralization, phenomena such as solidification will occur during distillation, resulting in a decrease in yield.
これらのことよりソデイウムボロノ１イドライド等の還
元試薬による方法は工業的に有利な方法とは言い難い。For these reasons, it is difficult to say that the method using a reducing reagent such as sodium boronohydride is an industrially advantageous method.
（ｉｌ［を解決するための手段）
本発明は一般式［１］ ：
［式中、Ｒ％は炭素数１〜１０の脂肪族炭化水素基、ア
ラルキル基、アリール基又は炭素数１〜５の低級アルコ
キシカルボニル基を示すｓＲ２は水素原子又は炭素数１
〜４の低級アルキル基を示す］で示される１−置換−３
−ピロリジノン類を水の存在下水素化触媒としてラネー
触媒を用い接触還元することを特徴とする一般式［２］
：［式中、Ｒ１及びＲ２は前記に同じ］で示される１
−置換−３−ヒドロキシピロリジン類の製造方法を提供
するものである。(Means for Solving il) The present invention is based on the general formula [1]: [wherein R% is an aliphatic hydrocarbon group having 1 to 10 carbon atoms, an aralkyl group, an aryl group having 1 to 5 carbon atoms] sR2 representing a lower alkoxycarbonyl group is a hydrogen atom or has 1 carbon number
~4 lower alkyl group] 1-substituted-3
- General formula [2] characterized by catalytic reduction of pyrrolidinones using a Raney catalyst as a hydrogenation catalyst in the presence of water
: 1 represented by [wherein R1 and R2 are the same as above]
A method for producing -substituted-3-hydroxypyrrolidines is provided.
前記式［１］で示される１−置換−３−ピロリジノン類
に於いて、Ｒ８が炭素数１〜１０の脂肪族炭化水素基を
表わすときにはＲ１は例えば、メチル基、エチル基、イ
ソプロピル基、ブチル基、イソブチル基、ｔｓ ｒｔ−
ブチル基、シクロペンチル基、シクロヘキシル基、シク
ロヘプチル基等の直鎖状、分岐状又は環状のアルキル基
である。In the 1-substituted-3-pyrrolidinones represented by the above formula [1], when R8 represents an aliphatic hydrocarbon group having 1 to 10 carbon atoms, R1 is, for example, a methyl group, an ethyl group, an isopropyl group, a butyl group. group, isobutyl group, ts rt-
It is a linear, branched or cyclic alkyl group such as a butyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, etc.
Ｒ１がアラルキル基又はアリール基を表わすときにはＲ
１は例えば、ベンジル基、クロルベンジル基、ブロモベ
ンジル基、フェネチル基、シンナモイル基等である。Ｒ
１がアルコキシカルボニル基を表わすときにはＲ１は例
えば、メトキシカルボニル基、エトキシカルボニル基、
イソプロポキシカルボニル基、ブトキシカルボニル基、
ｔａｒｔ−ブトキシカルボニル基等であるｓＲ２が炭素
数１〜４の低級アルキル基を表わすときにはＲ２は例え
ば、メチル基、エチル基、プロピル基、ブチル基、イソ
ブチル基、５ｅａ−ブチル基、ｔｅｒｔ−ブチル基等の
直鎖状又は分岐状のアルキル基である。When R1 represents an aralkyl group or an aryl group, R
Examples of 1 include a benzyl group, a chlorobenzyl group, a bromobenzyl group, a phenethyl group, and a cinnamoyl group. R
When 1 represents an alkoxycarbonyl group, R1 is, for example, a methoxycarbonyl group, an ethoxycarbonyl group,
Isopropoxycarbonyl group, butoxycarbonyl group,
When sR2 such as tart-butoxycarbonyl group represents a lower alkyl group having 1 to 4 carbon atoms, R2 is, for example, a methyl group, ethyl group, propyl group, butyl group, isobutyl group, 5ea-butyl group, tert-butyl group. It is a straight chain or branched alkyl group such as.
反応時に使用する水の量は１−置換−３−ピロリジノン
類に対し０．０ｌ−ＬＯ重量倍、好ましくは０．１−３
倍である０反応は無有機溶媒で行なうことが望ましいが
有機溶媒を使用することもできる。この時反応に使用す
る溶媒としてはメタノール、エタノール、イソプロパツ
ール等のアルコール類；ベンゼン、トルエン、キシレン
、シクロヘキサン等の炭化水素類を用いることができる
。The amount of water used during the reaction is 0.0 l-LO times the weight of the 1-substituted-3-pyrrolidinone, preferably 0.1-3 times the weight of the 1-substituted-3-pyrrolidinone.
It is preferable to carry out the 0 reaction using an inorganic solvent, but an organic solvent can also be used. As the solvent used in this reaction, alcohols such as methanol, ethanol and isopropanol; hydrocarbons such as benzene, toluene, xylene and cyclohexane can be used.
使用する溶媒が例えばベンゼン、トルエン等の炭化水素
類又は無溶媒のときには、反応系は有機層と水の分液状
態となっている。この状態でも反応はすみやかに進行し
目的物を収率良く与える、反応時に水を使用しない場合
、例えばメタノール溶媒のみで反応を行うと水素吸取速
度は遅くさらに副反応（目的物の脱水反応、縮合（２量
化）反応）により高沸生成物を生じ、目的物の収率は低
いものとなる。この高沸生成物は、反応系内に水が存在
しないため、１度生成した１−置換−；３−ヒドロキシ
ピロリジンが脱水、縮合等を起こして生じたものと推定
される。When the solvent used is a hydrocarbon such as benzene or toluene, or no solvent, the reaction system is in a state of separation of an organic layer and water. Even in this state, the reaction proceeds quickly and gives the target product in good yield.If water is not used during the reaction, for example, if the reaction is carried out using only methanol solvent, the hydrogen absorption rate is slow and further side reactions (dehydration reaction, condensation reaction of the target product) (dimerization) reaction) produces a high-boiling product, resulting in a low yield of the target product. This high-boiling product is presumed to be produced by dehydration, condensation, etc. of the 1-substituted-;3-hydroxypyrrolidine that has been generated once, since water is not present in the reaction system.
本発明に於いて、水はケトンの還元反応を促進しさらに
生成した目的物の副反応を抑制するという２つの重要な
役割を担っている。In the present invention, water plays two important roles: promoting the reduction reaction of ketones and suppressing side reactions of the generated target products.
本反応に使用するラネー触媒としては好ましくはラネー
ニッケル、ラネーコバルトである。ラネー触媒の量は１
−！換−３−ピロリジノン類に対し１−５０重量％、好
ましくは５−３０ を量％である。The Raney catalyst used in this reaction is preferably Raney nickel or Raney cobalt. The amount of Raney catalyst is 1
-! The amount is 1-50% by weight, preferably 5-30% by weight, based on the substituted-3-pyrrolidinones.
本反応における水素圧は常圧〜ｌ ５０ ｋｇ／ａｍ”
好ましくは５−６０ Ｋｇ／ｃ１２である。The hydrogen pressure in this reaction is from normal pressure to 50 kg/am.
Preferably it is 5-60 Kg/c12.
次に反応温度はＯ’−１５０℃好ましくは２０−１００
℃であり１反応時間は反応温度、水の使用量、触媒量に
より適宜選択することができるが通常０．５〜４時間で
ある。Next, the reaction temperature is O'-150℃, preferably 20-100℃.
℃, and one reaction time can be appropriately selected depending on the reaction temperature, the amount of water used, and the amount of catalyst, but is usually 0.5 to 4 hours.
本発明方法において生成した１−置換−３−ヒドロキシ
ピロリジン類の単離、精製は、反応終了後触媒のる別、
溶媒及び水の留去を行なった後蒸留により容易に行なう
ことができる。Isolation and purification of the 1-substituted-3-hydroxypyrrolidines produced in the method of the present invention can be carried out by removing the catalyst after the reaction is completed,
This can be easily carried out by distillation after removing the solvent and water.
（実施例）
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。(Examples) The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples.
実施例１
容量１リツターの電磁攪拌式オートクレーブに１〜ベン
ジル−３−ピロリジノン１７５ｇ、ラネーニッケル１７
．５ｇを仕込みざらに水１７５ｇを加えた後、これに水
素を導入および加熱して５０℃、４０ｋｇ／ｃｍ２に昇
温昇圧し、ついで当該温度、該圧力を保ちながら水素の
導入を続ζす接触還元反応を行なった。水素吸取は水素
導入開始後１時間で終了した。Example 1 In a 1-liter electromagnetic stirring autoclave, 175 g of 1-benzyl-3-pyrrolidinone and 17 Raney nickel were added.
．． After adding 175 g of water to the colander, hydrogen was introduced and heated to raise the temperature and pressure to 50°C and 40 kg/cm2, and then continued to introduce hydrogen while maintaining the temperature and pressure. A reduction reaction was performed. Hydrogen absorption was completed 1 hour after the start of hydrogen introduction.
反応終了後オートクレーブを室温まで冷却し、反応液か
ら触媒をろ別したのち、水を留去し残液を茄留して１−
ベンジル−３−ヒドロキシピロリジン１６５．５ｇ（収
率９３．４％）を得た。このものをガスクロマトグラフ
ィーにより分析したところ９９．５％の純度であった。After the reaction was completed, the autoclave was cooled to room temperature, the catalyst was filtered off from the reaction solution, water was distilled off, and the remaining liquid was distilled off to obtain 1-
165.5 g (yield 93.4%) of benzyl-3-hydroxypyrrolidine was obtained. This product was analyzed by gas chromatography and found to be 99.5% pure.
沸点：１４４〜ｂ
実施例２
触媒をラネーコバルトとした他は実施例１と同様に反応
及び後処理を行ない１−ベンジル−３−ヒドロキシピロ
リジンをｘ６１．３ｇ（’ＩＲ率９１．０％）得た。Boiling point: 144-b Example 2 The reaction and post-treatment were carried out in the same manner as in Example 1 except that Raney cobalt was used as the catalyst, and 61.3 g of 1-benzyl-3-hydroxypyrrolidine ('IR rate 91.0%) was obtained. Ta.
実施例３
水の量を１７．５．とじた他は実施４ｓｌと同様に反応
および後処理を行ない１−ベンジル−３−ヒドロキシピ
ロリジンを１６０．４ｇ （収率９０゜５％）得た。Example 3 The amount of water was 17.5. Other than closing, the reaction and post-treatment were carried out in the same manner as in Example 4sl to obtain 160.4 g (yield: 90.5%) of 1-benzyl-3-hydroxypyrrolidine.
実施例４
溶媒としてメタノール８７Ｋを加えた他は実施例］、と
同様に反応および後処理を行ない１−ベンジル−３−ヒ
ドロキシピロリジン１５２．１ｇ（収率８５．８％）を
得た。Example 4 152.1 g (yield: 85.8%) of 1-benzyl-3-hydroxypyrrolidine was obtained by carrying out the reaction and post-treatment in the same manner as in Example 4, except that methanol 87K was added as a solvent.
実施例５
溶媒としてトルエン８７ｇを加えた他は実施例１と同様
に反応および後処理を行ないｌ−ベンジル−３−ヒドロ
キシピロリジン１４４．８＆（ＩＩＸ２率８５．８％）
を得た。Example 5 The reaction and post-treatment were carried out in the same manner as in Example 1, except that 87 g of toluene was added as a solvent, and 144.8% of l-benzyl-3-hydroxypyrrolidine was obtained (IIX2 ratio: 85.8%).
I got it.
実施例６
１−ベンジル−３−ピロリジノンのかわりに１−ブチル
−３−ピロリジノン１４１ｇ （１モル）を用いラネー
ニッケル１４．１ｇ、水１４１ｇとした他は実施例１と
同様に反応および後処理を行なった。目的物である１−
ブチル−３−ヒドロキシピロリジンを１２１．６ｇ （
収率８５％）で得た。Example 6 The reaction and post-treatment were carried out in the same manner as in Example 1, except that 141 g (1 mol) of 1-butyl-3-pyrrolidinone was used instead of 1-benzyl-3-pyrrolidinone, and 14.1 g of Raney nickel and 141 g of water were used. Ta. 1- which is the object
121.6g of butyl-3-hydroxypyrrolidine (
Yield: 85%).
実施例７
１−ベンジル−３−ピロリジノンのかわりに１−カルボ
エトキシ−３−ピロリジノン１５７ｇ（１モル）を用い
う木−ニッケル１５．７ｇ、Ａ１５７ｇとした他は実施
例１と同様に反応および後処理を行なった。目的物であ
る１−カルボエトキシ−３−ヒドロキシピロリジンを１
３０．５＆（収率８５％）で得た。Example 7 The reaction and post-treatment were carried out in the same manner as in Example 1, except that 157 g (1 mol) of 1-carboethoxy-3-pyrrolidinone was used instead of 1-benzyl-3-pyrrolidinone, 15.7 g of wood-nickel was used, and 157 g of A was used. Processed. The target product, 1-carboethoxy-3-hydroxypyrrolidine, is
30.5% (yield: 85%).
比較例１
溶媒としてメタノール１７７ｇを用い７水を共存させな
い条件にしたほかは実施例１と同様に反応および後処理
を行なった。水素吸収は３時間程度ｍ続したが終点は明
確ではなかった。〕、−〕ベンジルー３−ヒドロキシピ
ロリジン８１．１ｇ（ｆＸ２率４５．７％）を得た他に
高沸生成物４３．９゜と若干の原料を回収した。Comparative Example 1 The reaction and post-treatment were carried out in the same manner as in Example 1, except that 177 g of methanol was used as the solvent and conditions were made such that no water was allowed to coexist. Hydrogen absorption continued for about 3 hours, but the end point was not clear. ], -] In addition to obtaining 81.1 g of benzy-3-hydroxypyrrolidine (fX2 ratio: 45.7%), 43.9° of a high-boiling product and some raw materials were recovered.
比較例２
溶媒をトルエンにかえた他は比較例１と同様に反応およ
び後処理を行なったが、水素の吸収はみられず原料を回
収した。Comparative Example 2 The reaction and post-treatment were carried out in the same manner as in Comparative Example 1 except that the solvent was changed to toluene, but no hydrogen absorption was observed and the raw material was recovered.
（発明の効果）
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１−置！ａ−３−ヒドロキシピロリジン
類を煩雑な後処理をすることなく容易に、高純度かつ取
率よく製造することができる。(Effects of the Invention) According to the present invention, 1-position compound is useful as a raw material for synthesis of raw materials and intermediates of pharmaceuticals, agricultural chemicals, etc. A-3-hydroxypyrrolidines can be easily produced with high purity and high yield without complicated post-treatment.
特許出覇人 広栄化学工業株式会社Patent winner Koei Chemical Industry Co., Ltd.
Claims (1)
アラルキル基、アリール基又は炭素数１〜５の低級アル
コキシカルボニル基を示す。Ｒ＿２は水素原子又は炭素
数１〜４の低級アルキル基を示す］で示される１−置換
−３−ピロリジノン類を水の存在下水素化触媒としてラ
ネー触媒を用いて接触還元することを特徴とする 一般式［２］： ▲数式、化学式、表等があります▼［２］ ［式中、Ｒ＿１及びＲ＿２は前記に同じ］で示される１
−置換−３−ヒドロキシピロリジン類の製造方法。[Claims] General formula [1]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [1] [In the formula, R_1 is an aliphatic hydrocarbon group having 1 to 10 carbon atoms,
It represents an aralkyl group, an aryl group, or a lower alkoxycarbonyl group having 1 to 5 carbon atoms. R_2 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms] is catalytically reduced using a Raney catalyst as a hydrogenation catalyst in the presence of water. General formula [2]: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [2] 1 shown by [In the formula, R_1 and R_2 are the same as above]
-Method for producing substituted-3-hydroxypyrrolidines.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1080390A JP2762107B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 1-substituted-3-hydroxypyrrolidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1080390A JP2762107B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 1-substituted-3-hydroxypyrrolidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02258763A true JPH02258763A (en) | 1990-10-19 |
| JP2762107B2 JP2762107B2 (en) | 1998-06-04 |
Family
ID=13716962
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1080390A Expired - Fee Related JP2762107B2 (en) | 1989-03-30 | 1989-03-30 | Method for producing 1-substituted-3-hydroxypyrrolidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2762107B2 (en) |
-
1989
- 1989-03-30 JP JP1080390A patent/JP2762107B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2762107B2 (en) | 1998-06-04 |
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