WO1997043256A1 - Process for the preparation of 3-hydroxypyrrolidine - Google Patents
Process for the preparation of 3-hydroxypyrrolidine Download PDFInfo
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- WO1997043256A1 WO1997043256A1 PCT/JP1997/001620 JP9701620W WO9743256A1 WO 1997043256 A1 WO1997043256 A1 WO 1997043256A1 JP 9701620 W JP9701620 W JP 9701620W WO 9743256 A1 WO9743256 A1 WO 9743256A1
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- Prior art keywords
- hydroxypyrrolidine
- hydroxy
- compound
- proline
- iii
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- 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
- C07D207/10—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 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
- C07D207/12—Oxygen or sulfur atoms
Definitions
- the present invention relates to a method for producing optically active 3- (R) -hydroxypyrrolidine useful as a raw material for medicines, agricultural chemicals and the like.
- Japanese Patent Publication No. 110452/1990 discloses a method of performing a decarboxylation reaction using trans-14-hydroxy-1-L-proline as a starting material to obtain 3- (R) -hydroxypyrrolidine in one step.
- This method is a decarboxylation reaction using vinyl ketones as a catalyst, and offers a milder and safer method than the conventional decarboxylation method, but there is a problem in industrial application due to the specialty of the catalyst. .
- An object of the present invention is to use cis-3-hydroxy-L-proline or trans-14-hydroxy L-proline as a starting material, and to prepare 3- (R) -hydrogen more easily than a conventional method without using a catalyst. It is to provide a method for producing xypyrrolidine.
- Cis-3-hydroxy-1-L-proline is an isomer of trans-4-hydroxy-L-proline, and its industrial production method is described in JP-A-7-322885.
- the present inventors have found that the cis-l-hydroxy-l-proline can be easily heated in an alcoholic solvent without adding any catalyst, and can be easily decarboxylated to give 3- (R) -hydroxyl in a high yield.
- the inventors have paid attention to being converted into pyrrolidine, and have reached the present invention. This method is also applicable to trans-14-hydroxy-1-L-proline, and similarly, 3- (R) -hydroxypyrrolidine can be obtained.
- the present invention relates to a compound of the formula (I) Or formula (II)
- the decarboxylation reaction in the present invention is carried out in the presence or absence of a solvent, but is preferably carried out in the presence of an alcohol.
- alcohols used in the reaction include alcohols having a boiling point of 120 ° C or more, such as octanol, hexanol, and cyclohexanol.
- the reaction is preferably carried out after charging the starting materials and, if necessary, the solvent, preferably with nitrogen or acetonitrile. Heating and stirring are performed in an inert gas atmosphere such as rugon.
- the reaction temperature any temperature of about 120 to 250 ° C is selected, and preferably around 140 to 160 ° C.
- the product is isolated from the reaction mixture by, for example, precipitation as a hydrogen halide salt or by distillation, and if necessary, extraction, washing, drying, concentration, recrystallization, column chromatography, or column chromatography. It is purified by a purification method commonly used in organic synthetic chemistry such as chromatography.
- hydrogen halide gas is directly blown into the reaction mixture, or an alcohol such as methanol, ethanol, isopropanol, octanol or the like containing hydrogen halide, or an organic compound such as ethyl acetate.
- an alcohol such as methanol, ethanol, isopropanol, octanol or the like containing hydrogen halide, or an organic compound such as ethyl acetate.
- the desired product is precipitated by adding a solvent.
- 3- (R) -Hydroxypyrrolidine obtained according to the present invention can be used as a synthetic intermediate for certain antibacterial agents, antidepressants, bronchodilators, analgesics, antiarrhythmic agents, etc. [Heterocycle (Heterocycles), 26, 2247 (1987)].
- trans-4-hydroxy-1-L-proline 20 mg was suspended in 1 ml of hexane, and the mixture was heated and stirred at about 156 ° C. in an argon atmosphere. After 6 hours, water and methanol were added to the reaction mixture to make a homogeneous solution, which was quantified by a high performance liquid chromatography internal standard method. As a result, the yield of the desired product was 4%, and the residual ratio of trans-4-hydroxy-L-phosphorus, which is a starting material, was 89%.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
Abstract
An easier and simpler process for preparing 3-(R)-hydroxypyrrolidine (III), characterized by using cis-3-hydroxy-L-proline (I) or trans-4-hydroxy-L-proline (II) as the starting compound and heating it without any catalyst to conduct decarboxylation.
Description
明細書 Specification
3—ヒドロキシピロリジンの製造法 Method for producing 3-hydroxypyrrolidine
技術分野 Technical field
本発明は、医薬、農薬等の原料として有用な光学活性な 3—（R)—ヒドロキシピロリ ジンの製造法に関する。 The present invention relates to a method for producing optically active 3- (R) -hydroxypyrrolidine useful as a raw material for medicines, agricultural chemicals and the like.
背景技術 Background art
光学活性なヒドロキシピロリジンおよびその誘導体の製造方法については、ヘテロ サイクルズ（Heterocycles)、 26卷、 2247頁（1 987年）の総説に数種類の方法が記 載されている。さらに、 4ーァミノ一 1 , 2—ブタンジオール一 1一スルホネートの環化 反応による方法（特開平 3— 1 76462 )および 1一アミノー 4—クロロー 2—ブタノール の環化反応による方法（特開平 2— 85249 )が知られている。しかしながら、これらの 製造方法では、数段階の反応ステップを要する、比較的高価な試薬を必要とする、光 学活性な原料を調製するのに手間がかかる等、その工業的応用には問題がある。 Several methods for producing optically active hydroxypyrrolidine and its derivatives are described in a review by Heterocycles, Vol. 26, p. 2247 (1987). Further, a method based on a cyclization reaction of 4-amino-1,1,2-butanediol-11-sulfonate (JP-A-3-176462) and a method based on a cyclization reaction of 1-1-amino-4-chloro-2-butanol (Japanese Patent Laid-Open Publication No. 85249) is known. However, these production methods have problems in their industrial application, such as requiring several reaction steps, requiring relatively expensive reagents, and taking time to prepare optically active raw materials. .
—方、発酵生産物であるヒドロキシプロリンを出発原料として脱炭酸反応を行なうこ とによるヒドロキシピロリジンの合成は、反応が一段階であることから、工業的応用が容 易であると考えられる。実際に、トランス一 4ーヒドロキシ一L—プロリンを出発原料とし て脱炭酸反応を行ない、一段階で 3— (R)ーヒドロキシピロリジンを得る方法が特公平 4一 1 0452に開示されている。この方法は、ビニルケトン類を触媒とする脱炭酸反応 であり、従来の脱炭酸の方法に比べて温和かつ安全な方法を提供しているが、触媒 の特殊性から工業的応用には問題がある。 同じくトランス一 4—ヒドロキシ— L一プロリ ンを出発原料とし、ァリールケトンを触媒として脱炭酸反応を行わせる方法（特開平 5 一 255204)力 S知られており、この方法では、工業生産規模での触媒入手の困難性お よび安定性の面で特公平 4— 1 0452における問題点を改良している。しかしながら、 触媒を使用しなければならない問題点は残る。 On the other hand, the synthesis of hydroxypyrrolidine by performing a decarboxylation reaction using hydroxyproline, which is a fermentation product, as a starting material, is considered to be easy for industrial application because the reaction is a single step. Practically, Japanese Patent Publication No. 110452/1990 discloses a method of performing a decarboxylation reaction using trans-14-hydroxy-1-L-proline as a starting material to obtain 3- (R) -hydroxypyrrolidine in one step. This method is a decarboxylation reaction using vinyl ketones as a catalyst, and offers a milder and safer method than the conventional decarboxylation method, but there is a problem in industrial application due to the specialty of the catalyst. . Similarly, a method is known in which trans-4-hydroxy-L-proline is used as a starting material and a decarboxylation reaction is carried out using aryl ketone as a catalyst (Japanese Patent Application Laid-Open No. 5-255204). It has improved the problems of Japanese Patent Publication No. 4-10452 in terms of catalyst availability and stability. However, the problem of having to use a catalyst remains.
発明の開示 Disclosure of the invention
本発明の目的は、 シス一 3—ヒドロキシー L一プロリンもしくはトランス一 4ーヒドロキ シー L一プロリンを出発原料とし、無触媒で、従来の方法よりも簡便に 3—（R)—ヒドロ
キシピロリジンを製造する方法を提供することにある。 An object of the present invention is to use cis-3-hydroxy-L-proline or trans-14-hydroxy L-proline as a starting material, and to prepare 3- (R) -hydrogen more easily than a conventional method without using a catalyst. It is to provide a method for producing xypyrrolidine.
シス一 3—ヒドロキシ一 L—プロリンはトランスー4ーヒドロキシー L一プロリンの異性 体であり、その工業的製造方法は特開平 7— 322885に記載されている。本発明者ら は、該シス一 3—ヒドロキシ一L一プロリンがアルコール溶媒中で加熱するだけで、何 ら触媒を加えることなく容易に脱炭酸反応により高収率で 3—（R)—ヒドロキシピロリジ ンに変換されることに着目し、本発明に至った。また、本法は、トランス一 4ーヒドロキ シ一 L一プロリンにも適用可能であり、 同様に 3—（R)—ヒドロキシピロリジンを得ること ができる。 Cis-3-hydroxy-1-L-proline is an isomer of trans-4-hydroxy-L-proline, and its industrial production method is described in JP-A-7-322885. The present inventors have found that the cis-l-hydroxy-l-proline can be easily heated in an alcoholic solvent without adding any catalyst, and can be easily decarboxylated to give 3- (R) -hydroxyl in a high yield. The inventors have paid attention to being converted into pyrrolidine, and have reached the present invention. This method is also applicable to trans-14-hydroxy-1-L-proline, and similarly, 3- (R) -hydroxypyrrolidine can be obtained.
本発明は、式（I )
または式（II) The present invention relates to a compound of the formula (I) Or formula (II)
HQ, HQ,
(ID (ID
C02H で表されるヒドロキシー L一プロリン類を無触媒で加熱し脱炭酸反応を行なうことを特 徴とする式（III) C0 2 The hydroxy-L one proline represented by H and heated in the absence of a catalyst formula for the feature to be carried out decarboxylation (III)
(,,,) ( ,,,)
次に、本発明について詳細に説明する。 Next, the present invention will be described in detail.
本発明における脱炭酸反応は、溶媒の存在下または非存在下で行なわれるが、好 ましくはアルコール類の存在下で行なわれる。反応に用いるアルコール類としては、 例えばォクタノール、へキサノ一ル、シクロへキサノーノレ等の沸点 1 20°C以上のアル コール類が挙げられる。 The decarboxylation reaction in the present invention is carried out in the presence or absence of a solvent, but is preferably carried out in the presence of an alcohol. Examples of alcohols used in the reaction include alcohols having a boiling point of 120 ° C or more, such as octanol, hexanol, and cyclohexanol.
反応は、 出発原料および必要により溶媒を仕込んだ後、好ましくは窒素もしくはァ
ルゴン等の不活性ガス雰囲気下で加熱撹拌することにより行なう。反応温度は、 120 〜250°C程度の任意の温度が選択されるが、好ましくは 140〜160°C付近である。反 応終了後、生成物は反応混合物より、例えばハロゲン化水素塩として析出させるか、 または蒸留する等の方法により単離され、必要に応じて抽出、洗浄、乾燥、濃縮、再 結晶、カラムクロマトグラフィー等の有機合成化学で常用される精製法によって精製さ れる。ハロゲン化水素塩として単離する場合には、例えば反応混合物に直接ハロゲン 化水素ガスを吹き込むかまたはハロゲン化水素を含有するメタノール、エタノール、ィ ソプロパノール、ォクタノール等のアルコール類、酢酸ェチル等の有機溶媒を添加す ることにより目的物を析出させる。 The reaction is preferably carried out after charging the starting materials and, if necessary, the solvent, preferably with nitrogen or acetonitrile. Heating and stirring are performed in an inert gas atmosphere such as rugon. As the reaction temperature, any temperature of about 120 to 250 ° C is selected, and preferably around 140 to 160 ° C. After the reaction is completed, the product is isolated from the reaction mixture by, for example, precipitation as a hydrogen halide salt or by distillation, and if necessary, extraction, washing, drying, concentration, recrystallization, column chromatography, or column chromatography. It is purified by a purification method commonly used in organic synthetic chemistry such as chromatography. When isolated as a hydrogen halide salt, for example, hydrogen halide gas is directly blown into the reaction mixture, or an alcohol such as methanol, ethanol, isopropanol, octanol or the like containing hydrogen halide, or an organic compound such as ethyl acetate. The desired product is precipitated by adding a solvent.
本発明により得られる 3— (R)—ヒドロキシピロリジンは、例えばある種の抗菌剤、抗 うつ剤、気管支拡張剤、鎮痛剤、抗不整脈剤等の合成中間体として供することができ る [ヘテロサイクルズ（Heterocycles)、 26卷、 2247頁（ 1987年）]。 3- (R) -Hydroxypyrrolidine obtained according to the present invention can be used as a synthetic intermediate for certain antibacterial agents, antidepressants, bronchodilators, analgesics, antiarrhythmic agents, etc. [Heterocycle (Heterocycles), 26, 2247 (1987)].
以下に、実施例および比較例により本発明をさらに詳細に説明する力 本発明は、 この実施例によって限定されるものではない。 EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. The present invention is not limited to the Examples.
発明を実施するための最良の形態 BEST MODE FOR CARRYING OUT THE INVENTION
実施例 1 Example 1
3—（R)—ヒドロキシピロリジン塩酸塩 3- (R) -hydroxypyrrolidine hydrochloride
シス一 3—ヒドロキシ一 L—プロリン 5. 0gを 1—へキサノーノレ 250mlに懸濁し、了 ルゴン雰囲気下 156°C付近で加熱撹拌した。 6時間後反応混合物は均一な溶液とな つた。この溶液を氷冷し、塩化水素 2. 7gを含むイソプロパノール 6. 75mlを加え、氷 冷下に 30分間撹拌した。溶媒をエバポレーターで留去後、残渣をイソプロパノール 5 0mlに加熱溶解し、酢酸ェチル 50mlを加えた。析出した結晶を濾過し、減圧乾燥す ることにより、 3— (R)—ヒドロキシピロリジン塩酸塩 3. 8g (収率 81%)を得た。 5.0 g of cis-3-hydroxy-1-L-proline was suspended in 250 ml of 1-hexanol, and heated and stirred at about 156 ° C. in a argon atmosphere. After 6 hours, the reaction mixture became a homogeneous solution. The solution was ice-cooled, 6.75 ml of isopropanol containing 2.7 g of hydrogen chloride was added, and the mixture was stirred under ice-cooling for 30 minutes. After evaporating the solvent with an evaporator, the residue was dissolved by heating in 50 ml of isopropanol, and 50 ml of ethyl acetate was added. The precipitated crystals were filtered and dried under reduced pressure to obtain 3.8 g (yield 81%) of 3- (R) -hydroxypyrrolidine hydrochloride.
(1) 融点 109.6 °C (1) Melting point 109.6 ° C
(2) "H-N R (DMSO-de) δ (ppm) ： 1.84-1.95 (2H, m), 2.97-3.23 (4H, m), 4.37 (1H， m), 9.6 (1H, broad). (2) "HNR (DMSO-d e ) δ (ppm): 1.84-1.95 (2H, m), 2.97-3.23 (4H, m), 4.37 (1H, m), 9.6 (1H, broad).
(3) IR (KBr) v (cm—1) : 3356, 3011, 1384, 1202, 955.
on (3) IR (KBr) v (cm— 1 ): 3356, 3011, 1384, 1202, 955. on
(4) [a]D = —8.05° (c = 3.5, メタノ一ノレ）. (4) [a] D = —8.05 ° (c = 3.5, methanole).
実施例 2 Example 2
3—（R)—ヒドロキシピロリジン 3- (R) -hydroxypyrrolidine
トランス一 4—ヒドロキシ一 L—プロリン 20mgを 1一へキサノール lmlに懸獨し、ァ ルゴン雰囲気下 156°C付近で加熱撹拌した。 6時間後反応混合物に水およびメタノ ールを加えて均一溶液とし、高速液体クロマトグラフィー内部標準法で定量した。その 結果、 目的物の生成率は 4%であり、出発原料であるトランス— 4—ヒドロキシ— Lープ 口リンの残存率は 89%であった。 20 mg of trans-4-hydroxy-1-L-proline was suspended in 1 ml of hexane, and the mixture was heated and stirred at about 156 ° C. in an argon atmosphere. After 6 hours, water and methanol were added to the reaction mixture to make a homogeneous solution, which was quantified by a high performance liquid chromatography internal standard method. As a result, the yield of the desired product was 4%, and the residual ratio of trans-4-hydroxy-L-phosphorus, which is a starting material, was 89%.
産業上の利用可能性 Industrial applicability
本発明により、従来の方法よりも簡便な 3— (R)—ヒドロキシピロリジンの製造法を提 供することができる。
According to the present invention, a method for producing 3- (R) -hydroxypyrrolidine that is simpler than the conventional method can be provided.
Claims
(1)式（υ
Equation (1) (υ
または式（II)
Or formula (II)
で表されるヒドロキシー L一プロリン類を無触媒で加熱し脱炭酸反応を行なうことを特 徴とする式（III)
A formula (III) characterized in that a hydroxy-L-proline represented by
で表される 3— (R)—ヒドロキシピロリジン [以下、式（1)、式（II)および式（III)で表さ れる化合物をそれぞれ化合物（I)、化合物（II)および化合物（III)という]の製造法。 3- (R) -Hydroxypyrrolidine represented by the following formula: [Hereinafter, compounds represented by formula (1), formula (II) and formula (III) are referred to as compound (I), compound (II) and compound (III), respectively. Manufacturing method.
(2)化合物 U)を無触媒で加熱し脱炭酸反応を行なうことを特徴とする化合物（III)の 製造法。 (2) A method for producing a compound (III), wherein the compound U) is heated without a catalyst to carry out a decarboxylation reaction.
(3)化合物（Π)を無触媒で加熱し脱炭酸反応を行なうことを特徴とする化合物（III) の製造法。 (3) A method for producing a compound (III), wherein the compound (III) is heated without a catalyst to carry out a decarboxylation reaction.
(4)アルコール類を溶媒として用いる範囲（1)〜（3)記載の 3— (R)—ヒドロキシピロ リジンの製造法。
(4) The process for producing 3- (R) -hydroxypyrrolidine according to the range (1) to (3), wherein an alcohol is used as a solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU27882/97A AU2788297A (en) | 1996-05-14 | 1997-05-14 | Process for the preparation of 3-hydroxypyrrolidine |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11912796 | 1996-05-14 | ||
| JP8/119127 | 1996-05-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997043256A1 true WO1997043256A1 (en) | 1997-11-20 |
Family
ID=14753616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP1997/001620 WO1997043256A1 (en) | 1996-05-14 | 1997-05-14 | Process for the preparation of 3-hydroxypyrrolidine |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2788297A (en) |
| WO (1) | WO1997043256A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1535904A2 (en) * | 2003-11-28 | 2005-06-01 | L'oreal | Process for the preparation of optically active 1-(4-nitrophenyl)-3-pyrrolidinole derivatives, paraphenylenediaines comprising chiral pyrrolidinyl groups |
| WO2007011162A1 (en) * | 2005-07-20 | 2007-01-25 | Chiroad Incorporate | Synthetic method of optically pure (s)-3-hydroxypyrrolidine |
| US7223873B2 (en) | 2004-03-30 | 2007-05-29 | Daisco Co., Ltd | Process for preparing amines |
| EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
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| JPS6023328A (en) * | 1983-07-19 | 1985-02-05 | Sankyo Co Ltd | Decarbonation reaction |
| JPH02111761A (en) * | 1988-10-20 | 1990-04-24 | Kyowa Hakko Kogyo Co Ltd | Production of uracil |
| JPH03123779A (en) * | 1989-10-07 | 1991-05-27 | Nippon Synthetic Chem Ind Co Ltd:The | Production of 5-(4-pyridyl)oxazole |
| JPH03161462A (en) * | 1989-11-20 | 1991-07-11 | Occidental Chem Corp | Preparation of 2, 4, 5-trifluorobenzoic acid by decarboxylating 3, 4, 6-trifluorophthalic acid anhydride |
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-
1997
- 1997-05-14 WO PCT/JP1997/001620 patent/WO1997043256A1/en active Application Filing
- 1997-05-14 AU AU27882/97A patent/AU2788297A/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6023328A (en) * | 1983-07-19 | 1985-02-05 | Sankyo Co Ltd | Decarbonation reaction |
| JPH02111761A (en) * | 1988-10-20 | 1990-04-24 | Kyowa Hakko Kogyo Co Ltd | Production of uracil |
| JPH03123779A (en) * | 1989-10-07 | 1991-05-27 | Nippon Synthetic Chem Ind Co Ltd:The | Production of 5-(4-pyridyl)oxazole |
| JPH03161462A (en) * | 1989-11-20 | 1991-07-11 | Occidental Chem Corp | Preparation of 2, 4, 5-trifluorobenzoic acid by decarboxylating 3, 4, 6-trifluorophthalic acid anhydride |
| JPH05255204A (en) * | 1992-03-11 | 1993-10-05 | Kanegafuchi Chem Ind Co Ltd | Production of amines |
Non-Patent Citations (1)
| Title |
|---|
| CHEMISTRY LETTERS, No. 6, (1986), HASHIMOTO, MITSUNORI et al., "A Novel Decarboxylation of alpha-Amino Acids. A Facile Method of Decarboxylation by the Use of 2-Cyclohexen-1-One as a Catalyst", Refer to p. 893-896. * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1535904A2 (en) * | 2003-11-28 | 2005-06-01 | L'oreal | Process for the preparation of optically active 1-(4-nitrophenyl)-3-pyrrolidinole derivatives, paraphenylenediaines comprising chiral pyrrolidinyl groups |
| FR2862970A1 (en) * | 2003-11-28 | 2005-06-03 | Oreal | PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE 16 (4-NITROPHENYL) -3-PYRROLIDINOL DERIVATIVES AND CHIRAL PYROLIDINYL GROUP PARAPHENYLENEDIAMINES |
| EP1535904A3 (en) * | 2003-11-28 | 2005-07-13 | L'oreal | Process for the preparation of optically active 1-(4-nitrophenyl)-3-pyrrolidinole derivatives, paraphenylenediaines comprising chiral pyrrolidinyl groups |
| US7223873B2 (en) | 2004-03-30 | 2007-05-29 | Daisco Co., Ltd | Process for preparing amines |
| WO2007011162A1 (en) * | 2005-07-20 | 2007-01-25 | Chiroad Incorporate | Synthetic method of optically pure (s)-3-hydroxypyrrolidine |
| US7652152B2 (en) | 2005-07-20 | 2010-01-26 | Chiroad Incorporate | Synthetic method of optically pure (S)-3-hydroxypyrrolidine |
| EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
| WO2024121219A1 (en) | 2022-12-07 | 2024-06-13 | Bayer Consumer Care Ag | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
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| Publication number | Publication date |
|---|---|
| AU2788297A (en) | 1997-12-05 |
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