WO2008026527A1 - Procédé de fabrication d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels - Google Patents

Procédé de fabrication d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels Download PDF

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Publication number
WO2008026527A1
WO2008026527A1 PCT/JP2007/066515 JP2007066515W WO2008026527A1 WO 2008026527 A1 WO2008026527 A1 WO 2008026527A1 JP 2007066515 W JP2007066515 W JP 2007066515W WO 2008026527 A1 WO2008026527 A1 WO 2008026527A1
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WO
WIPO (PCT)
Prior art keywords
group
substituted
carbon atoms
formula
unsubstituted
Prior art date
Application number
PCT/JP2007/066515
Other languages
English (en)
Japanese (ja)
Inventor
Kazumi Okuro
Masaru Mitsuda
Original Assignee
Kaneka Corporation
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 Kaneka Corporation filed Critical Kaneka Corporation
Priority to JP2008532046A priority Critical patent/JPWO2008026527A1/ja
Publication of WO2008026527A1 publication Critical patent/WO2008026527A1/fr

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Classifications

    • 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the present invention relates to a novel process for producing 3-cyanopyrrolidine derivatives and salts thereof which are useful compounds in various fields including the pharmaceutical field.
  • the DBU base used is very expensive, and there is a problem in terms of cost when it is carried out on an industrial scale.
  • DBU is a strong base that promotes the elimination reaction, and by-production of olefins due to cyanation and elimination at the 3-position may occur.
  • Illustrative V reaction is cyanation of N-Boc-3-toluenesulfonyloxypyrrolidine, but this reaction system can be used in, for example, optically active N-benzylthio-3-methanesulfonyloxy.
  • the present invention it is possible to easily produce a 3-cyanpyrrolidine derivative useful as a pharmaceutical intermediate and a salt thereof with high optical purity with high safety.
  • the 3-cyanopyrrolidine derivative was obtained in the form of a salt, especially in a crystalline form, which made it easier to handle industrially.
  • Examples of the substituted or unsubstituted aryl group having 6 to 20 carbon atoms include a phenyl group,
  • R 1 is preferably a methyl group, an ethyl group or a benzyl group, and more preferably a benzyl group.
  • R 2 H is a -valent acid
  • R 2 is a monovalent anion
  • R 2 H is a divalent acid or a trivalent acid
  • R 2 is a divalent acid.
  • the reaction crystallization method is not particularly limited, and examples thereof include a method in which compound (4) is produced from compound (2) by the above-described method and precipitated in a reaction solvent. In this case, the crystal of the compound (4) can be obtained by filtering the precipitated crystal.
  • Examples of the cooling crystallization method include a method of crystallizing the solution by cooling the solution containing the compound (4).
  • the solution containing the compound (4) can be produced by dissolving the compound (4) in at least one solvent selected from the aforementioned organic solvents.
  • the cooling temperature is not particularly limited and is 10 ° C or less, preferably 0 ° C or less.
  • the lower limit is not particularly limited, but is preferably 70 ° C or higher, more preferably 40 ° C or higher. Particularly preferably, it is at least 20 ° C.
  • Examples of the concentration crystallization method include a method of crystallization by concentrating a solution containing the compound (4).
  • the compound (4) once isolated may be dissolved again in a solvent, and the crystallization may be performed to obtain a crystal to improve the purity.
  • the compound (4) thus obtained is a novel compound found by the inventors and is a useful compound that is used as a raw material for various pharmaceuticals.
  • the crystalline form of the compound (4) is a very useful compound that is easy to purify and industrially easy to handle. Needless to say, the crystalline form of the compound (4) is also a new crystal isolated by the present inventors for the first time.

Abstract

L'invention concerne un procédé de fabrication de manière simple, commerciale et sûre d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels, qui est utile en tant que produit pharmaceutique. L'invention concerne notamment un procédé selon lequel un dérivé de pyrrolidine comprenant un groupement partant à la position 3 est cyanisé en utilisant de l'acétone cyanohydrine en présence d'une base inorganique. L'invention concerne également un procédé selon lequel un dérivé de 3-cyanopyrrolidine est converti en sel, puis cristallisé. La présente invention permet de fabriquer commercialement de manière simple un dérivé de 3-cyanopyrrolidine.
PCT/JP2007/066515 2006-08-28 2007-08-27 Procédé de fabrication d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels WO2008026527A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2008532046A JPWO2008026527A1 (ja) 2006-08-28 2007-08-27 ３−シアノピロリジン誘導体およびその塩の製造方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006230841 2006-08-28
JP2006-230841 2006-08-28

Publications (1)

Publication Number Publication Date
WO2008026527A1 true WO2008026527A1 (fr) 2008-03-06

Family

ID=39135810

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2007/066515 WO2008026527A1 (fr) 2006-08-28 2007-08-27 Procédé de fabrication d'un dérivé de 3-cyanopyrrolidine ou d'un de ses sels

Country Status (2)

Country Link
JP (1) JPWO2008026527A1 (fr)
WO (1) WO2008026527A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3318908A (en) * 1962-06-18 1967-05-09 Robins Co Inc A H 3-cyanopyrrolidines
JPS632976A (ja) * 1986-06-09 1988-01-07 ストウフアー　ケミカル　カンパニー ある種の３−ベンゾイル−４−オキソラクタム
JPH02218664A (ja) * 1989-02-17 1990-08-31 Tokyo Kasei Kogyo Kk 光学活性な１ｈ−３−アミノピロリジン化合物の製造法
JPH02300187A (ja) * 1989-04-28 1990-12-12 Fujisawa Pharmaceut Co Ltd １―アザビシクロ［３．２．０］ヘプト―２―エン―２―カルボン酸化合物
WO1997041123A1 (fr) * 1996-04-26 1997-11-06 Sankyo Company, Limited Derives de 1-methylcarbapeneme
WO2002085855A1 (fr) * 2001-04-19 2002-10-31 Eisai Co., Ltd. Derives de 2-iminopyrrolidine
CN1651400A (zh) * 2004-11-17 2005-08-10 王旭 一种l－正缬氨酸的合成方法
JP2005343835A (ja) * 2004-06-04 2005-12-15 Dai Ichi Seiyaku Co Ltd ２，５−２置換光学活性ピロリジン誘導体の製造法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3318908A (en) * 1962-06-18 1967-05-09 Robins Co Inc A H 3-cyanopyrrolidines
JPS632976A (ja) * 1986-06-09 1988-01-07 ストウフアー　ケミカル　カンパニー ある種の３−ベンゾイル−４−オキソラクタム
JPH02218664A (ja) * 1989-02-17 1990-08-31 Tokyo Kasei Kogyo Kk 光学活性な１ｈ−３−アミノピロリジン化合物の製造法
JPH02300187A (ja) * 1989-04-28 1990-12-12 Fujisawa Pharmaceut Co Ltd １―アザビシクロ［３．２．０］ヘプト―２―エン―２―カルボン酸化合物
WO1997041123A1 (fr) * 1996-04-26 1997-11-06 Sankyo Company, Limited Derives de 1-methylcarbapeneme
WO2002085855A1 (fr) * 2001-04-19 2002-10-31 Eisai Co., Ltd. Derives de 2-iminopyrrolidine
JP2005343835A (ja) * 2004-06-04 2005-12-15 Dai Ichi Seiyaku Co Ltd ２，５−２置換光学活性ピロリジン誘導体の製造法
CN1651400A (zh) * 2004-11-17 2005-08-10 王旭 一种l－正缬氨酸的合成方法

Also Published As

Publication number Publication date
JPWO2008026527A1 (ja) 2010-01-21

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