WO2009080708A1 - Utilisation d'un composé énantiopur - Google Patents

Utilisation d'un composé énantiopur Download PDF

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Publication number
WO2009080708A1
WO2009080708A1 PCT/EP2008/067910 EP2008067910W WO2009080708A1 WO 2009080708 A1 WO2009080708 A1 WO 2009080708A1 EP 2008067910 W EP2008067910 W EP 2008067910W WO 2009080708 A1 WO2009080708 A1 WO 2009080708A1
Authority
WO
WIPO (PCT)
Prior art keywords
sulphonyl
enantiopure
pyroglutamic acid
use according
enantiomers
Prior art date
Application number
PCT/EP2008/067910
Other languages
English (en)
Inventor
Roland Callens
Ronan Gire
Cyrille Pousset
Original Assignee
Solvay (Société Anonyme)
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 Solvay (Société Anonyme) filed Critical Solvay (Société Anonyme)
Publication of WO2009080708A1 publication Critical patent/WO2009080708A1/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
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00—Separation of optically-active compounds

Definitions

  • the invention relates to use of an enantiopure compound and to a process for the manufacture of an enantiopure compound.
  • Drugs of the Future 2006 31(4) p. 314-319 describes optical resolution of 2-(aminomethyl)-3 ,4-dihydro-2H- 1 -benzopyrane with N-tosyl(L)-proline.
  • the present invention makes available a process which makes possible the manufacture of enantiopure compounds, in particular of enantiopure amino alcohols or ersters, in an economic way, in particular as regards the yields and optical purities of enantiopure compounds and the overall economics of the process.
  • the invention concerns in consequence the use of enantiopure N-sulphonyl pyroglutamic acid as resolving agent for the separation of enantiomers by crystallization or precipitation.
  • enantiopure is intended to denote a chiral compound essentially composed of one enantiomer.
  • Use is generally made of an enantiopure N-sulphonyl pyroglutamic acid having an enantiomeric excess of greater than or equal to 99 %. Preference is given to an enantiopure resolving agents having an enantiomeric excess of greater than or equal to 99.5 %.
  • the N-sulphonyl group is an alkylsulphonyl or arylsulphonyl group, preferably an arylsulphonyl group.
  • the p-toluenesulphonyl group is more particularly preferred.
  • the enantiopure N-sulphonyl pyroglutamic acid has (S)-conf ⁇ guration. In another embodiment, the enantiopure N-sulphonyl pyroglutamic acid has (R)-configuration.
  • the enantiopure N-sulphonyl pyroglutamic acid can be used for example for separation of enantiomers of a compound comprising a primary or secondary amino group. In one preferred embodiment, such compound is an aminoalcohol. In another preferred embodiment, such compound is an amino ester.
  • the enantiopure N-sulphonyl pyroglutamic acid is generally used for separation of enantiomers from a, for example racemic, mixture of enantiomers.
  • the quantity of enantiopure N-sulphonyl pyroglutamic acid used is generally from 1 to 3, preferably from 1 to 2 molar equivalents relative to the desired enantiomer. If appropriate, the enantiopure N-sulphonyl pyroglutamic acid can be partly replaced by a achiral carboxylic acid, e.g. formic acid. In that case, the quantity of enantiopure N-sulphonyl pyroglutamic acid used is at least 1 molar equivalents relative to the desired enantiomer.
  • the enantiopure N-sulphonyl pyroglutamic is generally dissolved in a polar organic solvent.
  • polar organic solvents include esters such as ethyl acetate, alcohols such as isopropanol and nitriles such as acetonitrile.
  • the N-sulphonyl pyroglutamic acid is manufactured by cyclization of N-sulphonyl glutamic acid in a reaction medium and is used as resolving agent without isolation from the reaction medium of the cyclization.
  • the invention also relates to a process for the manufacture of an enantiopure compound comprising the use according to the invention, in particular a process for the manufacture of an enantiopure compound capable of forming a diastereomeric salt or a diastereomeric complex with a N-sulphonyl pyroglutamic acid, starting from a mixture of enantiomers of the said compound, which comprises (a) providing a solution comprising an enantiopure N-sulphonyl pyroglutamic acid in accordance with the use according to the invention and the mixture of enantiomers of the said compound and (b) crystallizing or precipitating from said solution a diastereomeric salt or a diastereomeric complex of said compound with the N-sulphonyl pyroglutamic acid enriched in one of the enantiomers of said compound.
  • the process according to the invention makes it possible to obtain good results for the preparation of enantiomers of an enantiopure compound capable of forming a diastereomeric salt or a diastereomeric complex with a N-sulphonyl pyroglutamic acid.
  • the process according to the invention is particularly economical, as high crystallization/precipitation yields can be obtained.
  • initiation is carried out by cooling the solution.
  • initiation is carried out by introducing a seed material into the solution.
  • crystallization or precipitation is initiated by modifying the composition of the solution e.g. by adding a solvent.
  • the process according to the invention often further comprises recovering the crystallized or precipitated diastereomeric salt or diastereomeric complex and optionally recrystallizing it.
  • the enantiopure compound can be liberated from the crystallized or precipitated diastereomeric salt or diastereomeric complex by treatment with a strong acid such as a mineral acid e.g. aqueous HCl.
  • a strong acid such as a mineral acid e.g. aqueous HCl.
  • Diisopropyl urea DIU was then filtered and salts were washed with 6 eq. of acetonitrile.
  • the quantity of Pip-EtOH (Piperidine-2-ethanol) to introduce.
  • the salt's resolution was achieved with a ratio of 0.5 eq. pTos GIp-OH to 1 eq. of PipEtOH.
  • 1 eq of Piperidine-2-ethanol was dissolved in 25 eq of CH3CN and mixed with the pTos-Glu-OH solution at room temperature.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne l'utilisation d'un acide N-sulfonyl-pyroglutamique énantiopur comme agent de séparation destiné à séparer des énantiomères par cristallisation ou précipitation. Pas de figure.
PCT/EP2008/067910 2007-12-21 2008-12-18 Utilisation d'un composé énantiopur WO2009080708A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07150334 2007-12-21
EP07150334.6 2007-12-21

Publications (1)

Publication Number Publication Date
WO2009080708A1 true WO2009080708A1 (fr) 2009-07-02

Family

ID=39469277

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/067910 WO2009080708A1 (fr) 2007-12-21 2008-12-18 Utilisation d'un composé énantiopur

Country Status (1)

Country Link
WO (1) WO2009080708A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1183781A (en) * 1968-02-14 1970-03-11 Ici Ltd Resolution Process.
WO2005023838A1 (fr) * 2003-09-09 2005-03-17 Solvay (Société Anonyme) Procede de fabrication d'un compose enantiopure

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1183781A (en) * 1968-02-14 1970-03-11 Ici Ltd Resolution Process.
WO2005023838A1 (fr) * 2003-09-09 2005-03-17 Solvay (Société Anonyme) Procede de fabrication d'un compose enantiopure

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SWAN J M ET AL: "The synthesis of L-Glutaminyl-L-asparagine, L-GLUTAMINE AND L-ISOGLUTAMINE FROM P-TOLUENESULFONYL-L-GLUTAMIC ACID", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 76, 1 January 1954 (1954-01-01), pages 3110 - 3113, XP002269297, ISSN: 0002-7863 *

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