[go: up one dir, main page]

WO2018108797A1 - Procédé de préparation de l-glufosinate ou de ses sels au moyen d'éphédrine - Google Patents

Procédé de préparation de l-glufosinate ou de ses sels au moyen d'éphédrine Download PDF

Info

Publication number
WO2018108797A1
WO2018108797A1 PCT/EP2017/082190 EP2017082190W WO2018108797A1 WO 2018108797 A1 WO2018108797 A1 WO 2018108797A1 EP 2017082190 W EP2017082190 W EP 2017082190W WO 2018108797 A1 WO2018108797 A1 WO 2018108797A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
homoalanin
ephedrine
phosphinic acid
salt
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.)
Ceased
Application number
PCT/EP2017/082190
Other languages
German (de)
English (en)
Inventor
Peter BRÜCHNER
Christian Funke
Sandra LEHMANN
Jan SALMON
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer CropScience AG
Original Assignee
Bayer CropScience AG
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 Bayer CropScience AG filed Critical Bayer CropScience AG
Publication of WO2018108797A1 publication Critical patent/WO2018108797A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton

Definitions

  • the invention relates primarily to a process for the preparation of L-glufosinate or its salts using ephedrine, in particular the preparation of L-glufosinate or its salts by (dynamic kinetic) racemate resolution. Furthermore, the invention relates to certain salts of glufosinate and ephedrine and the use of ephedrine for the (dynamic kinetic) resolution of DL-glufosinate or its salts.
  • DL-Ia 2-amino-4- (hydroxy-methyl-phosphoryl) butanoic acid
  • DL-Ib ammonium salt
  • the L-form can be obtained by enzymatic transamination, as described for example in DE3920570, DE3923650, EP0249188 or WO2007 / 100101.
  • CN103275896 a Bacillus cereus strain is used to produce the L-form in high optical purity. Also processes for the preparation of the L-form by asymmetric hydrogenation are known, for example from EP0238954, EP1864989 or EP2060578.
  • No. 4,647,692 describes the resolution of the amino acids 4-hydroxy-phenylglycine and 3,4-dihydroxyphenylglycine by precipitation with (+) - 3-bromo-camphor-10-sulfonic acid in the presence of ketones and organic acids, such as acetic acid. In general terms, this method is also recommended for the racemate resolution of (DL-Ia).
  • J. Org. Chem. 1983, 48, 843-846 describes the racemization of D-amino acids in acetic acid or other organic carboxylic acids in the presence of catalytic amounts of aliphatic or aromatic aldehydes.
  • No. 4,520,205 describes processes for the separation of the enantiomers of racemic 2,3-dihydroindole-2-carboxylic acid by means of ephedrine.
  • US 5,767,309 and US 5,869,668 (corresponding to WO 95/23805) is described on an industrial scale racemic resolution method of [DL] -Homoalanin-4-yl- (methyl) phosphinic acid (DL-Ia) or their salts are described, where the chiral bases quinine, cinchonine, cinchonidine or brucine are described as suitable, however, the use of (+) - 3-bromo-camphor-8-sulfonic acid was not suitable.
  • the above-mentioned methods have one or more disadvantages, from a process engineering and / or economic point of view, such as e.g. poor accessibility of the necessary (heterocyclic) intermediates and / or the use of organometallic agents,
  • Solids handling such as crystallization or precipitation or filtration - Filtration and the handling of solids are among the most time-consuming and therefore expensive steps of a process.
  • the invention relates to a process for the preparation of [L] -homoalanin-4-yl- (methyl) phosphinic acid (L-acid) and / or salts thereof, characterized in that it comprises the following steps: a) providing homoalanine-4 -yl- (methyl) phosphinic acid and / or salts thereof containing 20% by weight or more of [D] -homoalanin-4-yl- (methyl) phosphinic acid (D-acid) and / or salts thereof, respectively and based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and b) reacting the D-acid provided in step a) and / or their salts with ephedrine in water or in an aqueous-organic solvent mixture, wherein optionally in addition one, several or all of the following steps c) to e) carried out c) in the case that the free L-acid is prepared, neutralization of the obtained
  • Um salting with a base d) addition of one or more organic solvents, and / or e) separation of the phase containing [L] -Homoalanin-4-yl- (methyl) phosphinic acid (L-acid) and / or salts thereof.
  • the process of the invention does not require any special techniques and purification operations, such as necessary in enzymatic transamination, but may be carried out in any conventional industrial chemical plant.
  • the essential differences and process-technological or economic advantages of the process according to the invention compared to the process described in WO 95/23805 are mainly that at no point in the process according to the invention, a solids handling or filtration is necessary because no crystallization must be carried out, whereby the inventive method itself especially suitable for continuous process control.
  • the ephedrine used in the process according to the invention can be separated after completion of the reaction, for example by extraction and, preferably after purification by distillation, again in the inventive method can be used, ie the ephedrine is recyclable.
  • ephedrine is significantly cheaper compared to, for example, quinine and is available in a quantity which is necessary for a large-scale process, ie in sufficient quantity.
  • the process according to the invention is preferably carried out by using homoalanin-4-yl (methyl) phosphinic acid and / or salts thereof at a content of 30% by weight or more, preferably 40% by weight or more, preferably of 45% by weight or more of [D] -homoalanin-4-yl- (methyl) phosphinic acid (D-acid) and / or salts thereof, in each case based and calculated on the total amount of homoalanine used in step a) 4-yl- (methyl) phosphinic acid.
  • the process of the invention is carried out in such a way that [D] -Homoalanin-4-yl- (methyl) phosphinic acid (D-acid) and / or salts thereof is racemized.
  • the process according to the invention is carried out in such a way that the racemic compound [DL] -homoalanin-4-yl- (methyl) phosphinic acid (DL-acid) and / or salts thereof are used in the racemate resolution.
  • a preferred process according to the invention is characterized in that [DL] -homoalanin-4-yl- (methyl) phosphinic acid (DL-acid) and / or salts thereof are used in step a).
  • Glufosinate ie the free 2-amino-4- [hydroxy (methyl) phosphinoyl] butanoic acid
  • glufosinate salts preferably the sodium, disodium, ammonium or diammonium salt
  • ephedrine preferably (-) - ephedrine
  • ephedrine is used for the production of L-glufosinate.
  • other compounds structurally similar to ephedrine such as the diastereomeric pseudoephedrine, have been found
  • the process according to the invention can be carried out with (+) - ephedrine [(IS, 2R) -2-methylamino-1-phenylpropan-1-ol; CAS number 321-98-2], whereby also its salts or hydrates can be used, e.g. the hemihydrate (CAS number 144429-10-7), the hydrochloride (CAS number 24221-86-1) or the sulphate (CAS number 188661-03-2).
  • the inventive method is preferably with (-) - ephedrine [(lR, 2S) -2-methylamino-l-phenylpropan-lol; CAS number 299-42-3], wherein also its salts or hydrates can be used, for example the hemihydrate (CAS number 50906-05-3), the hydrochloride (CAS number 50-98-6) or the sulfate (CAS number 134-72-5).
  • the method according to the invention is therefore characterized in that the reaction is carried out with (-) - ephedrine.
  • the process according to the invention is preferably carried out in such a way that the total amount of ephedrine (preferably of (-) - ephedrine) in the reaction is 0.5 to 8 molar equivalents, preferably 0.8 to 6 molar equivalents, preferably 1 to 4 molar Equivalents, based in each case on the total amount of homoalanin-4-yl (methyl) phosphinic acid.
  • the process according to the invention is preferably carried out in such a way that the total amount of water in the reaction is 0.01 to 7 molar equivalents, preferably 0.05 to 6 molar equivalents, preferably 0.1 to 5 molar equivalents, in each case based on the used Total amount of homoalanin-4-yl (methyl) phosphinic acid. More preferred is a process according to the invention in which the total amount of water in the reaction is 0.25 to 5 molar equivalents, more preferably 0.5 to 4 molar equivalents, and most preferably 1 to 3 molar equivalents, based in each case total amount of homoalanin-4-yl (methyl) phosphinic acid used.
  • a process according to the invention is preferably carried out in such a way that no organic solvent (ie only water) or an aqueous-organic solvent mixture, ie a solvent mixture of water and one or more organic solvents is used in the reaction, these organic solvents preferably being selected from the group consisting of aromatic hydrocarbons, aliphatic hydrocarbons, saturated cyclic hydrocarbons, aliphatic alcohols, amides, ethers, esters, ketones and aliphatic nitriles, in turn, preferably C6-C9-aromatic hydrocarbons, aliphatic Cs-Cio-hydrocarbons, saturated cyclic Cs -Cs hydrocarbons, aliphatic C2-C6 alcohols and C3-C 7 ketones.
  • organic solvent ie only water
  • organic solvents ie an aqueous-organic solvent mixture
  • these organic solvents being selected from the group consisting of toluene and methyl tert-butyl ether (MTBE), xylene, cyclohexane, methylcyclohexane, n-hexane, n-heptane, THF (tetrahydrofuran), 2-methyltetrahydrofuran, DMF (dimethylformamide), DMAc (dimethylacetamide), acetonitrile, butyronitrile, ethyl acetate and aliphatic alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, 2-butanol, tert-butanol and 4-methyl-2-pentanol.
  • MTBE methyl tert-butyl ether
  • organic solvent ie only water
  • organic solvents ie an aqueous-organic solvent mixture
  • these organic solvents being selected from the group consisting of toluene, xylene, cyclohexane, Methylcyclohexane, n-hexane, n-heptane, n-butanol, n-propanol, i-propanol, ethanol, 4-methyl-2-pentanol, tert-butanol, i-butanol and 2-butanol.
  • a process according to the invention is preferably carried out in such a way that the reaction takes place in the presence of a catalytically effective amount of an aldehyde, the process according to the invention preferably being carried out without addition of an organic acid.
  • a process according to the invention is preferably carried out in such a manner that the reaction is carried out in the presence of 0.01 to 10 mol%, preferably 0.05 to 5 mol%, and particularly preferably 0.1 to 2.5 mol%. %, of a catalytically active aldehyde, in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid used.
  • Suitable catalytically active aldehydes are aliphatic aldehydes such as heptanal, aromatic aldehydes such as benzaldehyde, heteroaromatic aldehydes such as 2-pyridylaldehyde or salicylaldehydes such. Salicylaldehyde, 3,5-dichlorosalicylaldehyde, 3,5-dinitrosalicylaldehyde,
  • the process is carried out in the presence of a catalytically effective amount of a six-membered (hetero) aromatic aldehyde, which preferably has a hydroxy group in the 2-position to the aldehyde group and / or electron-withdrawing radicals in the 3- and / or 5-position to the aldehyde group, and optionally is further substituted.
  • a catalytically effective amount of a six-membered (hetero) aromatic aldehyde which preferably has a hydroxy group in the 2-position to the aldehyde group and / or electron-withdrawing radicals in the 3- and / or 5-position to the aldehyde group, and optionally is further substituted.
  • the process is carried out in the presence of 3,5-dichlorosalicylaldehyde and / or 5-nitrosalicylaldehyde.
  • the molar total amount of above-defined six-membered (hetero) aromatic aldehydes used in the process according to the invention is preferably in the range from 0.01 to 10 mol%, preferably 0.05 to 5 mol%, and particularly preferably 0.1 to 2.5 mol .-%, in each case based on total amount of homoalanin-4-yl (methyl) phosphinic acid.
  • the process according to the invention is characterized in that the reaction is carried out with 0.5 to 8 molar equivalents of (-) - ephedrine, the total amount of water in the reaction 0.01 to 7 molar equivalents, the reaction in the presence from 0.01 to 10 mol .-% of a catalytically active aldehyde, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl- (methyl) phosphinic acid, and the reaction at temperatures in the range of 40 to 150 ° C takes place.
  • the process according to the invention is characterized in that the reaction is carried out with 0.8 to 6 molar equivalents of (-) - ephedrine, the total amount of water in the reaction 0.05 to 6 molar equivalents, the reaction in Presence of 0.05 to 5 mol .-% of a catalytically active aldehyde, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and the reaction at temperatures in the range of 40 to 150 ° C takes place.
  • the process according to the invention is characterized in that the reaction is carried out with 0.8 to 6 molar equivalents of (-) - ephedrine, the total amount of water in the reaction 0.05 to 6 molar equivalents, the reaction in Presence of 0.05 to 5 mol .-% of a catalytically active six-membered (hetero) aromatic aldehyde takes place, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and the reaction is carried out at temperatures in the range of 50 to 120 ° C.
  • the process according to the invention is characterized in that the reaction is carried out with 0.8 to 6 molar equivalents of (-) - ephedrine, the total amount of water in the reaction 0.05 to 6 molar equivalents, the reaction in Presence of 0.1 to 2.5 mol .-% of a catalytically active six-membered (hetero) aromatic aldehyde is carried out, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and the reaction at Temperatures in the range of 50 to 120 ° C takes place.
  • the process according to the invention is characterized in that the reaction is carried out with 0.8 to 6 molar equivalents of (-) - ephedrine, the total amount of water in the reaction is 0, 1 to 5 molar equivalents, the reaction in Presence of 0.1 to 2.5 mol .-% of a catalytically active six-membered (hetero) aromatic aldehyde takes place, which has a hydroxy group in the 2-position to the aldehyde group and / or electron-withdrawing radicals in the 3- and / or 5-position to the aldehyde group , and optionally further substituted, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and the reaction is carried out at temperatures in the range of 60 to 100 ° C.
  • the process according to the invention is characterized in that the reaction is carried out with 1 to 4 molar equivalents of (-) - ephedrine, the total amount of water in the reaction is 0.25 to 5 molar equivalents, the reaction in the presence of 0.1 to 2.5 mol .-% of a catalytically active six-membered (hetero) aromatic aldehyde takes place, which is a hydroxy group in the 2-position to the aldehyde group and / or electron-withdrawing radicals in the 3- and / or 5-position to the aldehyde group, and optionally further substituted, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl (methyl) phosphinic acid, and the reaction is carried out at temperatures in the range of 60 to 100 ° C.
  • the process according to the invention is characterized in that the reaction is carried out with 1 to 4 molar equivalents of (-) - ephedrine, the total amount of water in the reaction 0.5 to 4 molar equivalents, the reaction in the presence of 0.1 to 2.5 mol .-% of 3,5-dichlorosalicylaldehyde and / or 5-nitrosalicylaldehyde, wherein the molar amounts are in each case based on the total amount of homoalanin-4-yl- (methyl) phosphinic acid, and the reaction at Temperatures in the range of 60 to 100 ° C takes place.
  • step c) is carried out, in which case a salification is carried out with a base, which is preferably selected from the group consisting of NH 3, NaOH or KOH or the aqueous solutions of these bases.
  • a base which is preferably selected from the group consisting of NH 3, NaOH or KOH or the aqueous solutions of these bases.
  • step d) for working up of the reaction mixture - depending on the desired product form - if not yet contained in the reaction mixture, an organic solvent or solvent mixture for ephedrine extraction are additionally added.
  • one or more organic solvents are preferably used in addition to the solvent 1 (mixture) optionally used in step b).
  • Suitable organic solvents which are preferably used in step d) are selected from toluene, methyl tert-butyl ether (MTBE), xylene, cyclohexane, methylcyclohexane, n-hexane, n-heptane, THF (tetrahydrofuran), 2-methyltetrahydrofuran, DMF ( Dimethylformamide), DMAc (dimethylacetamide), acetonitrile, butyronitrile, ethyl acetate and aliphatic alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, 2-butanol, tert-butanol and / or 4- methyl-2-pentanol.
  • MTBE methyl ter
  • the inventive method is suitable on an industrial scale, ie in the technical or industrial scale to be carried out.
  • 50 kg or more of glufosinate or glufosinate salt are used in a process according to the invention which is carried out in the batch process, preferably 100 kg or more, particularly preferably 250 kg or more.
  • the method according to the invention is also suitable for being carried out in a continuous mode of operation.
  • Step 1 Mixing racemic ammonium glufosinate (DL-Ib), ephedrine and water, and optionally an organic solvent or solvent mixture,
  • Step 2 Remove ammonia (NH3) and most of the water,
  • Step 3 Addition of a catalytically effective amount of an aldehyde, and reaction to
  • Step 4 Addition of aqueous ammonia solution or alkali lye, and optionally an organic solvent or solvent mixture,
  • Step 5 Extraction and separation of the aqueous product phase
  • Step 6 Replace the (preferably redistilled) ephedrine in step 1.
  • step 1 preferably 0.8 to 6 molar equivalents of ephedrine (preferably of (-) - ephedrine) are used, preferably 1 to 4 molar equivalents, each based on the total amount of homoalanin-4-yl (methyl) phosphinic acid.
  • ephedrine preferably of (-) - ephedrine
  • step 1 racemic ammonium glufosinate (DL-Ib) can be used as an aqueous solution.
  • one or more organic solvents may additionally be used.
  • any conventional organic solvents are possible, preferably toluene, methyl tert-butyl ether (MTBE), xylene, cyclohexane, methylcyclohexane, n-hexane, n-heptane, THF (tetrahydrofuran), 2-methyltetrahydrofuran, DMF (dimethylformamide), DMAc ( Dimethylacetamide), acetonitrile, butyronitrile, ethyl acetate and aliphatic alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, 2-butanol, tert-butanol and / or 4-methyl-2-pentanol ,
  • step 2 by applying a vacuum and / or heating the mixture, ammonia and most of the water can be removed. Preferably, less than 6 equivalents of water should remain in the residue, based on the total amount of homoalanin-4-yl (methyl) phosphinic acid used.
  • the total amount of water in the reaction is preferably at most 5 molar equivalents, more preferably at most 4 molar equivalents, and most preferably 1 to 3 molar equivalents, based in each case on the total amount of homoalanin-4-yl ( methyl) phosphinic acid.
  • Step 3 is preferably carried out in such a way that the reaction in the presence of 0.01 to 10 mol .-%, preferably 0.05 to 5 mol .-%, and particularly preferably 0.1 to 2.5 mol .-% , a catalytically active aldehyde, in each case based on total amount of homoalanin-4-yl (methyl) phosphinic acid, wherein aliphatic aldehydes such as heptanal, aromatic aldehydes such as benzaldehyde, heteroaromatic aldehydes such as 2-pyridylaldehyde or salicylaldehydes such as Salicylaldehyde, 3,5-dichlorosalicylaldehyde, 3,5-dinitrosalicylaldehyde, 2-hydroxypyridine-3-carbaldehyde, 4-hydroxypyridine-3-carbaldehyde, or also
  • step 3 is carried out in the presence of a catalytically effective amount of a six-membered (hetero) aromatic aldehyde, preferred are salicylaldehydes and heteroaromatic hydroxycarbaldehydes, more preferably 3,5-dichlorosalicylaldehyde and / or 5-nitrosalicylaldehyde.
  • a catalytically effective amount of a six-membered (hetero) aromatic aldehyde preferred are salicylaldehydes and heteroaromatic hydroxycarbaldehydes, more preferably 3,5-dichlorosalicylaldehyde and / or 5-nitrosalicylaldehyde.
  • the molar total amount of above-defined six-membered (hetero) aromatic aldehydes used in the process according to the invention is preferably in the range from 0.01 to 10 mol%, preferably 0.05 to 5 mol%, and particularly preferably 0.1 to 2.5 mol .-%, in each case based on total amount of homoalanin-4-yl (methyl) phosphinic acid.
  • the process is preferably carried out in such a manner that the reaction at temperatures in the range of 40 to 150 ° C, more preferably from 50 to 120 ° C, and particularly preferably at temperatures in the range of 60 to 100 ° C. is carried out.
  • step 4 the reaction mixture - depending on the desired product form - added aqueous alkali or aqueous ammonia solution for workup.
  • organic solvent may be additionally added for ephedrine extraction, e.g. Toluene, ethyl acetate or MTBE.
  • the ephedrine contained in the organic phase can be reused after distillation (in the same reaction), ie the ephedrine is recyclable.
  • a glufosinate salt such as ammonium glufosinate and glufosinate can be used as the free acid in step 1. In this case, step 2 of the method described above can be omitted.
  • the reaction time of the process according to the invention depends inter alia on a few parameters such as the reaction temperature and the reactor size.
  • the person skilled in the art will choose the optimum reaction time such that the desired result is achieved as economically as possible in terms of process.
  • the reaction time is usually in the range of 8 to 72 hours, frequently in the range of 12 to 60 hours, and usually in the range of 16 to 48 hours.
  • the process according to the invention can be carried out in such a way and it may be advantageous that first a mixture, a salt or a mixture of salts of ephedrine (preferably of (-) - ephedrine) and homoalanin-4-yl- (methyl) phosphinic acid is prepared before the reaction of the provided in step a) D acid and / or its salt, preferably in the form of the DL acid and / or its salt, to the desired L-acid and / or its salt.
  • ephedrine preferably of (-) - ephedrine
  • homoalanin-4-yl- (methyl) phosphinic acid is prepared before the reaction of the provided in step a) D acid and / or its salt, preferably in the form of the DL acid and / or its salt, to the desired L-acid and / or its salt.
  • mixtures, salts or mixtures of salts of ephedrine preferably of (-) - ephedrine
  • L-homoalanin-4-yl (methyl) phosphinic acid which are formed by the reaction in the process according to the invention are advantageous.
  • the present invention further relates to a mixture, a salt or a mixture of salts of ephedrine and homoalanin-4-yl (methyl) phosphinic acid, wherein mixtures, salts or mixtures of salts of (-) - ephedrine and homoalanine-4 yl (methyl) phosphinic acid are preferred.
  • Mixtures preferred according to the invention can be obtained, for example, by mixing homoalanin-4-yl (methyl) phosphinic acid and ephedrine, preferably (-) - ephedrine, with one another.
  • the molar amount of ephedrine is preferably in the range of 0.5 to 4, preferably in the range of 0.75 to 3, more preferably in the range of 1 to 2, in each case based on the molar amount of homoalanin-4-yl (methyl) phosphinic acid used.
  • Salts according to the invention or salts of salts according to the invention can be obtained, for example, by dissolving homoalanin-4-yl (methyl) phosphinic acid and ephedrine, preferably (-) - ephedrine, in water, preferably at a temperature in the range from 10 to 100 ° C, preferably at a temperature in the range of 20 to 80 ° C, and then the resulting solution is concentrated, ie, the water is removed from this solution.
  • the molar amount of ephedrine is preferably in the range of 0.5 to 4, preferably in the range of 0.75 to 3, more preferably in the range of 1 to 2, in each case based on the molar amount of homoalanin-4-yl (methyl) phosphinic acid used.
  • Preferred according to the invention is a salt or a mixture of salts selected from the group consisting of
  • the present invention relates to the use of ephedrine, preferably of (-) - ephedrine,
  • rac-glufosinate racemic glufosinate, corresponding to [DL] -homoalanin-4-yl (methyl) phosphinic acid (DL-Ia)
  • D-Glufosinate [D] -Homoalanin-4-yl (methyl) phosphinic acid (D-Ia)
  • L-Glufosinate [L] -Homoalanin-4-yl- (methyl) phosphinic acid (L-Ia)
  • rpm revolutions per Minute
  • NMR quantitative NMR spectroscopy
  • aqueous phase 81.4 g HPLC: 85:15 L: D; quant. NMR: 24.7% disodium glufosinate, 81% yield).
  • the organic phase was concentrated (67.3 g quant. NMR: 97.1% ephedrine, 92% recovery).
  • Example 6 To 9.1 g of (-) - ephedrine (2 eq), 4.3 g of ethanol and 0.47 g of water at 75 ° C in a 100 mL multi-neck flask with a KPG stirrer and reflux condenser 5 g of rac-glufosinate ( 1 eq, free acid), then 0.053 g of 3,5-dichlorosalicylaldehyde, and the resulting mixture was stirred at 75 ° C for 16 h. A sample of the suspension was then dissolved in 20% aqueous NaOH, washed with dichloromethane and then analyzed by chiral HPLC: 77:23 L: D.
  • Example 10 20 g of rac-glufosinate (1 eq, free acid) were added to 73 g of (-) - ephedrine (4 eq) and 2 ml of water in a Flexi-Lab reactor at 95 ° C. jacket temperature and stirred at 300 rpm. After 1 h, 211 mg of 3,5-dichlorosalicylaldehyde (1 mol%) were added and stirred overnight. The reaction was cooled to 75 ° C internal temperature after 24 h and 53 mL of 20% NaOH added. The phases were separated at 50 ° C: aqueous phase (78.5 g quant. NMR: 29.2% disodium glufosinate; 92% yield; 86:14 L: D); the organic phase was concentrated (74.95 g quant. NMR: 92.4% ephedrine;> 95% recovery).
  • Example 11 40 g of a 50% aqueous solution of rac-ammonium glufosinate were admixed with 61 g of (-) - ephedrine and concentrated under reduced pressure at 60 ° C. and 5 mbar. The liquid at 60 ° C residue with 81 g total weight was then heated in a Flexi-Lab reactor with anchor agitator to 95 ° C jacket temperature and stirred at 300 rpm. 177 mg of 3,5-dichlorosalicylaldehyde was added and the resulting mixture was stirred overnight. The batch was cooled after 48 h to 75 ° C internal temperature, mixed with 21 mL of 25% ammonia solution and 100 mL of toluene.
  • Example 16 In a Flexi-Lab reactor with anchor stirrer, 20 g of rac-glufosinate (free acid) were added to 73 g (-) - ephedrine and 4 mL of water at 95 ° C jacket temperature. After 1 h, 234 mg of 3,5-dinitro-salicylaldehyde were added and the mixture was stirred at 95.degree. After 24 h, a sample was analyzed by chiral HPLC: 58:42 L: D.
  • Example 17 Example 17:
  • Example 19 4.1 g of rac-glufosinate (1 eq, free acid) and 3.74 g of D - (+) - ephedrine (1 eq) were dissolved in 0.95 g of water (2.5 eq) and 8.6 g n-propanol at 20 ° C presented. 432 mg of 3,5-dichlorosalicylaldehyde (10 mol%) were added and the resulting mixture was stirred overnight. The suspension was filtered and a sample was measured by chiral HPLC (57:43 L: D).
  • Example 20 25 g of rac-glufosinate (1 eq, free acid) were mixed with 57.3 g (-) - ephedrine (99.5%, 2.5 eq), 25.4 g toluene (2 eq) and 5 g of water (2 eq) in a Flexi-Lab reactor with an anchor stirrer stirred at 300 rpm and heated to 85 ° C jacket temperature. After 1 h, 264 mg of 3,5-dichlorosalicylaldehyde (1 mol%) added and stirred at 85 ° C overnight.
  • the batch was cooled to 55 ° C internal temperature after 16 h, treated with 65 g of toluene and then added to 70.5 g of 10% aqueous ammonia solution.
  • the phases were separated at 55 ° C., giving 94.5 g of aqueous phase (quant., NMR: 29.7% ammonium glufosinate, 94% yield, 95: 5 L: D).
  • the organic phase was concentrated (59.3 g quant. NMR: 95.2% ephedrine, 99% recovery).
  • Example VI Comparative Example with (+) - pseudoephedrine
  • Example C2 Comparative Example with (S) -1-phenylethylamine 20 g of rac-glufosinate (free acid) were added to 53.5 g of (S) - (-) - 1-phenylethylamine in a Flexi-Lab reactor at 95 ° C. mL of water. After addition of 0.21 g of 3,5-dichloro-salicylaldehyde, the mixture was stirred at a jacket temperature of 95.degree. C. and 300 rpm overnight. After 24 h, a sample was measured by chiral HPLC: 49:51 L: D.
  • Example S4 According to standard procedure 2 above, the salt of (-) - ephedrine and [D] -homoalanin-4-yl (methyl) phosphinic acid (2: 1 salt) was prepared from D-glufosinate and (-) - ephedrine.
  • Example S5 According to standard procedure 2 above, the salt of (-) - ephedrine and [L] -homoalanin-4-yl (methyl) phosphinic acid (2: 1 salt) was prepared from L-glufosinate and (-) - ephedrine.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)

Abstract

L'invention concerne principalement un procédé de préparation de L-glufosinate ou de ses sels au moyen d'éphédrine, en particulier la préparation de L-glufosinate ou de ses sels par résolution optique (dynamique cinétique). L'invention concerne en outre certains sels de glufosinate et d'éphédrine et l'utilisation d'éphédrine pour la résolution optique (dynamique cinétique) de DL-glufosinate ou de ses sels.
PCT/EP2017/082190 2016-12-15 2017-12-11 Procédé de préparation de l-glufosinate ou de ses sels au moyen d'éphédrine Ceased WO2018108797A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16204245.1 2016-12-15
EP16204245 2016-12-15

Publications (1)

Publication Number Publication Date
WO2018108797A1 true WO2018108797A1 (fr) 2018-06-21

Family

ID=57708341

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2017/082190 Ceased WO2018108797A1 (fr) 2016-12-15 2017-12-11 Procédé de préparation de l-glufosinate ou de ses sels au moyen d'éphédrine

Country Status (2)

Country Link
TW (1) TW201831500A (fr)
WO (1) WO2018108797A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019018406A1 (fr) * 2017-07-18 2019-01-24 Agrimetis, Llc Procédés de purification de l-glufosinate
US10260078B2 (en) 2016-03-02 2019-04-16 Agrimetis, Llc Methods for making L-glufosinate
WO2020214631A1 (fr) 2019-04-16 2020-10-22 Agrimetis, Llc Procédés de production de l-glufosinate d'ammonium monohydraté cristallin
WO2022041603A1 (fr) * 2020-08-26 2022-03-03 浙江工业大学 Procédé de préparation de poudre de l-glufosinate-ammonium
WO2022259267A1 (fr) * 2021-06-11 2022-12-15 Upl Limited Procédé d'obtention de l-glufosinate

Citations (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4168963A (en) 1976-05-17 1979-09-25 Hoechst Aktiengesellschaft Herbicidal agents
US4265654A (en) 1977-12-28 1981-05-05 Meiji Seika Kaisha Ltd. Herbicidal compositions
US4520205A (en) 1982-06-28 1985-05-28 American Home Products Corporation Chemical resolution of (+)-2,3-dihydroindole-2-carboxylic acid
US4521348A (en) 1978-11-11 1985-06-04 Hoechst Aktiengesellschaft Phosphorus-containing cyanohydrine derivatives
US4599207A (en) 1983-06-01 1986-07-08 Hoechst Aktiengesellschaft Process for the preparation of phosphorus-containing cyanohydrin derivatives
US4647692A (en) 1984-08-30 1987-03-03 Beecham Group P.L.C. Racemization and resolution of α-amino acids
EP0238954A2 (fr) 1986-03-22 1987-09-30 Hoechst Aktiengesellschaft Procédé de préparation de (dérivés de la) l-phosphinothricine ainsi que leurs esters alcoyliques
EP0249188A2 (fr) 1986-06-09 1987-12-16 Meiji Seika Kaisha Ltd. Procédé de production de l'acide L-2-amino-4-(hydroxyméthyl-phosphinyl)-butyrique
DE3920570A1 (de) 1989-06-23 1991-01-03 Hoechst Ag Verfahren zur isolierung von l-2-amino-4-methylphosphinobuttersaeure-ammoniumsalz aus einer enzymatischen transaminierungsloesung
DE3923650A1 (de) 1989-07-18 1991-01-31 Hoechst Ag Verfahren zur gewinnung von l-2-amino-4-methylphosphinobuttersaeure-(salzen) durch elektrodialyse
WO1995023805A1 (fr) 1994-03-04 1995-09-08 Hoechst Schering Agrevo Gmbh Procede de preparation d'acide homoalanin-4-yl-(methyl)phosphinique (l) ou (d) et de ses sels par decomposition racemique
US6359162B1 (en) 1997-08-20 2002-03-19 Hoechst Schering Agrevo Gmbh Method for producing glufosinates and intermediate products for the same
WO2007100101A1 (fr) 2006-03-02 2007-09-07 Meiji Seika Kaisha, Ltd. Gene de l'aspartate aminotransferase et procede de production de la l-phosphinothricine
EP1864989A1 (fr) 2005-03-29 2007-12-12 Meiji Seika Kaisha Ltd. Procede de production de l'acide l-2-amino-4-(hydroxymethylphosphinyl)butanoique
EP2060578A1 (fr) 2006-09-04 2009-05-20 Meiji Seika Kaisha Ltd. Procédé de fabrication d'un acide aminophosphinylbutanoïque optiquement actif
CN103275896A (zh) 2013-05-27 2013-09-04 浙江工业大学 蜡状芽孢杆菌及其在微生物转化制备l-草铵膦中的应用

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4168963A (en) 1976-05-17 1979-09-25 Hoechst Aktiengesellschaft Herbicidal agents
US4265654A (en) 1977-12-28 1981-05-05 Meiji Seika Kaisha Ltd. Herbicidal compositions
US4521348A (en) 1978-11-11 1985-06-04 Hoechst Aktiengesellschaft Phosphorus-containing cyanohydrine derivatives
US4520205A (en) 1982-06-28 1985-05-28 American Home Products Corporation Chemical resolution of (+)-2,3-dihydroindole-2-carboxylic acid
US4599207A (en) 1983-06-01 1986-07-08 Hoechst Aktiengesellschaft Process for the preparation of phosphorus-containing cyanohydrin derivatives
US4647692A (en) 1984-08-30 1987-03-03 Beecham Group P.L.C. Racemization and resolution of α-amino acids
EP0238954A2 (fr) 1986-03-22 1987-09-30 Hoechst Aktiengesellschaft Procédé de préparation de (dérivés de la) l-phosphinothricine ainsi que leurs esters alcoyliques
EP0249188A2 (fr) 1986-06-09 1987-12-16 Meiji Seika Kaisha Ltd. Procédé de production de l'acide L-2-amino-4-(hydroxyméthyl-phosphinyl)-butyrique
DE3920570A1 (de) 1989-06-23 1991-01-03 Hoechst Ag Verfahren zur isolierung von l-2-amino-4-methylphosphinobuttersaeure-ammoniumsalz aus einer enzymatischen transaminierungsloesung
DE3923650A1 (de) 1989-07-18 1991-01-31 Hoechst Ag Verfahren zur gewinnung von l-2-amino-4-methylphosphinobuttersaeure-(salzen) durch elektrodialyse
WO1995023805A1 (fr) 1994-03-04 1995-09-08 Hoechst Schering Agrevo Gmbh Procede de preparation d'acide homoalanin-4-yl-(methyl)phosphinique (l) ou (d) et de ses sels par decomposition racemique
US5767309A (en) 1994-03-04 1998-06-16 Hoechst Schering Agrevo Gmbh Processes for preparing L!- or D!-homoalanin-4-yl-(methyl)phosphinic acid and salts thereof by racemate resolution
US5869668A (en) 1994-03-04 1999-02-09 Hoechst Schering Agrevo Gmbh Processes for preparing L!- or D!-homoalanin-4-yl-(methyl) phosphinic acid and salts thereof by racemate resolution
US6359162B1 (en) 1997-08-20 2002-03-19 Hoechst Schering Agrevo Gmbh Method for producing glufosinates and intermediate products for the same
EP1864989A1 (fr) 2005-03-29 2007-12-12 Meiji Seika Kaisha Ltd. Procede de production de l'acide l-2-amino-4-(hydroxymethylphosphinyl)butanoique
WO2007100101A1 (fr) 2006-03-02 2007-09-07 Meiji Seika Kaisha, Ltd. Gene de l'aspartate aminotransferase et procede de production de la l-phosphinothricine
EP2060578A1 (fr) 2006-09-04 2009-05-20 Meiji Seika Kaisha Ltd. Procédé de fabrication d'un acide aminophosphinylbutanoïque optiquement actif
CN103275896A (zh) 2013-05-27 2013-09-04 浙江工业大学 蜡状芽孢杆菌及其在微生物转化制备l-草铵膦中的应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BULL. CHIM. SOC. JAP., vol. 56, 1983, pages 3744 - 3747
J. ORG. CHEM., vol. 48, 1983, pages 843 - 846

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11732281B2 (en) 2016-03-02 2023-08-22 Basf Se Methods for making L-glufosinate
US10260078B2 (en) 2016-03-02 2019-04-16 Agrimetis, Llc Methods for making L-glufosinate
US12305207B2 (en) 2016-03-02 2025-05-20 Basf Se Methods for making L-glufosinate
US10781465B2 (en) 2016-03-02 2020-09-22 Agrimetis, Llc Methods for making L-glufosinate
US12305206B2 (en) 2016-03-02 2025-05-20 Basf Se Methods for making L-glufosinate
US11913048B2 (en) 2016-03-02 2024-02-27 Basf Se Methods for making L-glufosinate
US11905538B2 (en) 2016-03-02 2024-02-20 Basf Se Methods for making L-glufosinate
US11560577B2 (en) 2016-03-02 2023-01-24 Basf Se Methods for making L-glufosinate
US11976089B2 (en) 2017-07-18 2024-05-07 Basf Se Methods for the purification of L-glufosinate
IL271990B2 (en) * 2017-07-18 2023-05-01 Agrimetis Llc Methods for the purification of l-glufosinate
US11634442B2 (en) 2017-07-18 2023-04-25 Basf Se Methods for the purification of L-glufosinate
US11897908B2 (en) 2017-07-18 2024-02-13 Basf Se Methods for the purification of L-glufosinate
US11897909B2 (en) 2017-07-18 2024-02-13 Basf Se Methods for the purification of L-glufosinate
WO2019018406A1 (fr) * 2017-07-18 2019-01-24 Agrimetis, Llc Procédés de purification de l-glufosinate
IL271990A (en) * 2017-07-18 2020-02-27 Agrimetis Llc Methods for the purification of L-glufosinate
US12234254B2 (en) 2019-04-16 2025-02-25 Basf Se Methods for producing crystalline L-glufosinate ammonium monohydrate
WO2020214631A1 (fr) 2019-04-16 2020-10-22 Agrimetis, Llc Procédés de production de l-glufosinate d'ammonium monohydraté cristallin
WO2022041603A1 (fr) * 2020-08-26 2022-03-03 浙江工业大学 Procédé de préparation de poudre de l-glufosinate-ammonium
US12465047B2 (en) 2020-08-26 2025-11-11 Zhejiang University Of Technology Preparation method for L-glufosinate-ammonium powder
WO2022259267A1 (fr) * 2021-06-11 2022-12-15 Upl Limited Procédé d'obtention de l-glufosinate

Also Published As

Publication number Publication date
TW201831500A (zh) 2018-09-01

Similar Documents

Publication Publication Date Title
WO2018108797A1 (fr) Procédé de préparation de l-glufosinate ou de ses sels au moyen d'éphédrine
EP0748325B1 (fr) Procede de preparation d'acide homoalanin-4-yl-(methyl)phosphinique [l] ou [d] et de ses sels par decomposition racemique
WO2018108794A1 (fr) Procédé de préparation de d-glufosinate ou de ses sels au moyen d'éphédrine
WO2002002532A1 (fr) Esters d'acide 4-alcoxycyclohexan-1-aminocarboxylique, et leur procede de production
EP0000518B1 (fr) Procédé de dédoublement chimique du racémate de l'acide mandélique
EP3655413B1 (fr) Fabrication de glufosinate par conversion de 3-[n-butoxy(méthyl)phosphoryl]-1-cyanopropylacétate en une mélange de n-butyl(3-amino-3-cyanopropyl)-méthylphosphinate et la sel d'ammonium d'acid phosphinique (3-amino-3-cyanopropyl)-méthyl
WO2014202441A1 (fr) Procédé de préparation de 2-chlorodialkylbenzylamines
DE602005003472T2 (de) Verfahren zur herstellung von 2-oxo-1-pyrrolidinderivaten durch intramolekulare allylierung
DE2735036A1 (de) Optisch aktive, n-substituierte pyrrolidine, verfahren zu ihrer herstellung und deren verwendung
CH639945A5 (de) Verfahren zur trennung von racemischen alpha-aminonitrilen.
DE2558508C3 (de) Verfahren zur Racematspaltung von DL-Pantolacton
EP1765766B1 (fr) Procede de production de 3-hydroxy-3-phenyle-propylamines enantiomeres
EP1968960B1 (fr) Separation racemique de 2,6-trans-dimethylmorpholine
DE2350610C3 (de) DL-Lithiumpantoat, D (+)-üthiumpantoat, L (-)-Lithiumpantoat und Verfahren zur Herstellung der optischen Antipoden des Pantolactons
EP0923534A1 (fr) Procede de preparation d'amines phenethyliques racemiques
EP0001821B1 (fr) Procédé de résolution de D,L-alpha-amino acides et les sels utilisés dans ce but
EP0906267B1 (fr) Procede pour produire des 1-phenylethylamines optiquement actives
WO2005005375A1 (fr) Procede pour produire des esters de l'acide 4-cyano-3-hydroxybutyrique
WO2004092119A2 (fr) Procede de production de derives de cysteine et de serine alpha-methyles
EP1046638B1 (fr) Procédé pour la préparation de dérivés d'aminoacides
DE10249339A1 (de) Verfahren zur Racematspaltung von 3-Aminopentannitril
DE19530205A1 (de) Verfahren zur Herstellung von optisch aktiven l-Aryl-alkylaminen
EP0049688B1 (fr) Procédé de préparation de N-cyanolactames
DE19530204A1 (de) Verfahren zur Herstellung von optisch aktiven l-Aryl-alkylaminen
DE102004035034A1 (de) Racematspaltung von p-Hydroxyphenyl-2-alkoxy-propionsäuren

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17829157

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17829157

Country of ref document: EP

Kind code of ref document: A1