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WO1999058493A2 - Procede de preparation de phenylalanine optiquement pure - Google Patents

Procede de preparation de phenylalanine optiquement pure Download PDF

Info

Publication number
WO1999058493A2
WO1999058493A2 PCT/EP1999/002862 EP9902862W WO9958493A2 WO 1999058493 A2 WO1999058493 A2 WO 1999058493A2 EP 9902862 W EP9902862 W EP 9902862W WO 9958493 A2 WO9958493 A2 WO 9958493A2
Authority
WO
WIPO (PCT)
Prior art keywords
phenylalanine
acetic acid
optically pure
preparation
mixture
Prior art date
Application number
PCT/EP1999/002862
Other languages
English (en)
Other versions
WO1999058493A3 (fr
Inventor
Pietro Allegrini
Giuseppe Barreca
Alessandro Rosi
Giorgio Soriato
Original Assignee
Zambon Group S.P.A.
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 Zambon Group S.P.A. filed Critical Zambon Group S.P.A.
Publication of WO1999058493A2 publication Critical patent/WO1999058493A2/fr
Publication of WO1999058493A3 publication Critical patent/WO1999058493A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/30—Preparation of optical isomers

Definitions

  • the present invention relates to a process for the preparation of optically pure phenylalanine and, more particularly, it relates to a process for the preparation of D- or L-phenylalanine by crystallisation of enantiomerically enriched mixtures.
  • D-phenylalanine and L-phenylalanine are widely known compounds (The Merck Index - XII ed., no. 7425, page 1253).
  • object of the present invention is a process for the preparation of optically pure phenylalanine consisting of the crystallisation in acetic acid of a mixture enantiomerically enriched in one of the two enantiomers.
  • optically pure phenylalanine means a phenylalanine with an enantiomeric excess (ee) higher than 99%.
  • the used acetic acid is glacial acetic acid.
  • the amount of acetic acid can vary from 2 to 10 times by weight with respect to the mixture to be purified, preferably from 3 to 8 times by weight.
  • the crystallisation procedure foresees first the dissolution into acetic acid of the mixture to be purified by heating to a temperature generally from 60°C to 90°C.
  • the crystallisation can be optionally seeded by adding a little amount of the desired phenylalanine in optically pure form.
  • the filtration of the crystallised product is generally carried out after keeping the mixture at room temperature for a period variable from some minutes to some hours.
  • the process of the present invention is particularly useful for the purification of enantiomerically enriched mixtures deriving from resolutions of D,L-phenylalanine by fractional crystallisation of diastereoisomeric salts but it can be efficiently used in every case an increase of the optical purity of a mixture enantiomerically enriched of one of the two phenylalanine enantiomers is desired.
  • the process object of the present invention allows to obtain D- phenylalanine or L-phenylalanine in optically pure form (ee>99%) with a single crystallisation though starting from a low optical purity, for example from mixtures with a
  • the resultant solution was cooled at 65°C before adding a little amount of L-phenylalanine as crystallisation seed.
  • the resultant solution was cooled at 55°C before adding a little amount of D-phenylalanine as crystallisation seed.
  • the resultant suspension was cooled at 20°C in about 1 hour and kept under these conditions for 18 hours.
  • the solid was filtered and washed with glacial acetic acid (2x5.5 g).
  • the resultant solution was cooled at 56-58°C before adding a little amount of D- phenylalanine as crystallisation seed.
  • the reactor and the filter were washed with hot glacial acetic acid (12 g at 80°C) and the washings were collected with the filtrate into a 250 ml flask with mechanic stirrer, thermometer and reflux condenser.
  • the product was brought into solution again at 90°C, let spontaneously cool up to 50°C under slow stirring and the solution was seeded with optically pure D-phenylalanine (0.05 g).
  • the mixture was heated at 70°C; the resultant solution was added with L4S charcoal (0.5 g) and the mixture was kept under stirring at 70°C for 30 minutes before filtering.
  • the filter was washed with hot glacial acetic acid (10 g at 70°C) and the washings were collected with the filtrate into a 250 ml flask with mechanic stirrer, thermometer and reflux condenser.
  • the solution was cooled up to 40°C and seeded with optically pure D- phenylalanine.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé de préparation de D- ou L-phénylalanine consistant à cristalliser un mélange enrichi, de manière énantiomorphe, dans l'un des deux éniantomères, à partir d'un acide acétique.
PCT/EP1999/002862 1998-05-11 1999-04-28 Procede de preparation de phenylalanine optiquement pure WO1999058493A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI98A001014 1998-05-11
ITMI981014 IT1299210B1 (it) 1998-05-11 1998-05-11 Processo per la preparazione di fenilalanina otticamente pura

Publications (2)

Publication Number Publication Date
WO1999058493A2 true WO1999058493A2 (fr) 1999-11-18
WO1999058493A3 WO1999058493A3 (fr) 2000-01-27

Family

ID=11379990

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/002862 WO1999058493A2 (fr) 1998-05-11 1999-04-28 Procede de preparation de phenylalanine optiquement pure

Country Status (2)

Country Link
IT (1) IT1299210B1 (fr)
WO (1) WO1999058493A2 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4262092A (en) * 1979-05-08 1981-04-14 Ethyl Corporation Process for producing N-acyl-D-phenylalanine ester
US4847409A (en) * 1988-12-14 1989-07-11 The Nutrasweet Company Recovery of L-amino acid isomers from their racemic mixtures

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4262092A (en) * 1979-05-08 1981-04-14 Ethyl Corporation Process for producing N-acyl-D-phenylalanine ester
US4847409A (en) * 1988-12-14 1989-07-11 The Nutrasweet Company Recovery of L-amino acid isomers from their racemic mixtures

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J. JACQUES, A. COLLET, S. H. WILLEN: "Enantiomers, Racemates, and Resolutions" 1991 , KRIEGER , MALABAR, US XP002122203 page 216 -page 225 *

Also Published As

Publication number Publication date
IT1299210B1 (it) 2000-02-29
ITMI981014A1 (it) 1999-11-11
WO1999058493A3 (fr) 2000-01-27

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