WO2009037230A2 - Procédé perfectionné pour préparer des esters (e)-2-(2-chlorométhylphényl)-2-alcoximinoacétique - Google Patents

Procédé perfectionné pour préparer des esters (e)-2-(2-chlorométhylphényl)-2-alcoximinoacétique Download PDF

Info

Publication number
WO2009037230A2
WO2009037230A2 PCT/EP2008/062261 EP2008062261W WO2009037230A2 WO 2009037230 A2 WO2009037230 A2 WO 2009037230A2 EP 2008062261 W EP2008062261 W EP 2008062261W WO 2009037230 A2 WO2009037230 A2 WO 2009037230A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
mixture
esters
reaction
cyclohexane
Prior art date
Application number
PCT/EP2008/062261
Other languages
English (en)
Other versions
WO2009037230A3 (fr
Inventor
Karsten Luettgen
Martin Lassnig
Original Assignee
Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg
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 Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg filed Critical Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg
Publication of WO2009037230A2 publication Critical patent/WO2009037230A2/fr
Publication of WO2009037230A3 publication Critical patent/WO2009037230A3/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/14—Separation; Purification; Stabilisation; Use of additives

Definitions

  • the present invention relates to an improved process for preparing (E)-2-(2-chloromethylphenyl)-2-alkoximinoacetic esters.
  • (E)-2-(2-Chloromethylphenyl)-2-alkoximinoacetic esters are important intermediates for the preparation of active agrochemical ingredients and/or microbicides of the methoximinophenylglyoxylic ester series, as described, for example, in EP 0 254 426, EP 0 782 982, WO 95/18789 and WO 95/21153.
  • methyl o-(N,N- dimethylaminomethyl)-phenylglyoxylate or methyl o-piperidinomethylphenylglyoxylate are obtained by reaction of N-benzyldimethylamine or N-benzylpiperidine with an organolithium compound and subsequent reaction with a dialkyl oxalate compound, with a chloroformic ester to give the corresponding o-chloromethylphenylglyoxylic esters, which are then oximated with o-methylhydroxlamine or hydroxylamine and then methylated, fluoromethylated or difluoromethylated and reacted with a chloroformic ester.
  • methyl (E)-2-(2-chloromethylphenyl)-2- methoximinoacetate is obtained, for example, by treating a solution of the (E/Z) isomer mixture of methyl 2-(2-chloromethylphenyl)-2-methoximinoacetate in methylcyclohexane with hydrogen chloride gas.
  • the present invention therefore provides an improved process for preparing (E)-2-(2-chloromethylphenyl)-2-alkoximinoacetic esters of the formula
  • R is a radical inert to the reaction, n is 0 to 4 and
  • R1 and R5 may each independently be C-i-C ⁇ -alkyl radicals, which comprises reacting a compound of the formula
  • n, R, R1 and R5 are each as defined above, then extracting with cyclohexane, then isomerizing the isomer mixture by introducing gaseous hydrochloric acid, neutralizing the reaction mixture and crystallizing the compound of the formula I using a cosolvent.
  • R is a radical inert to the reaction, i.e. the R radical can be selected as desired, provided that it is inert with respect to the reaction conditions.
  • the R radical can be selected as desired, provided that it is inert with respect to the reaction conditions.
  • Ci-Ci 2 -alkyl radicals preferably Ci-C 6 -alkyl radicals
  • Ci-Ci 2 -alkenyl radicals preferably Ci-C 6 -alkenyl radicals, Ci-Ci 2 -alkoxy radicals, preferably Ci-C 6 -alkoxy radicals, phenyl, benzyl, nitro, etc.
  • R1 and R5 are each independently a C-pCe-alkyl radical, for instance methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, tert-butyl, etc.
  • R1 and R5 are preferably each independently a C 1 -C 2 -alkyl radical, more preferably methyl.
  • the starting compound used for the process according to the invention is a compound of the formula (II) in which n, R, R and R1 are each as defined above.
  • the compound of the formula (II) is converted to the compound of the formula (III) by reaction with o- methylhydroxylammonium hydrochloride or sulfate.
  • o-methylhydroxylammonium hydrochloride or sulfate are added in the presence of a suitable solvent or solvent mixture at a temperature of from 0 0 C to 100 0 C, preferably from 20 0 C to 65°C.
  • the pH of the o-methylhydroxylammonium hydrochloride solution is adjusted by means of an inorganic base to from 0 to 7, preferably from 2.5 to 4.5.
  • Suitable solvents are, for example alcohol (R2OH)/water mixtures, where R2 is a C1 to C4 alkyl radical which may be linear or branched, or solvents such as DMF, acetonitrile, MTBE and mixtures thereof. Preference is given to using methanol/water or ethanol/water mixtures.
  • reaction solution is extracted with cyclohexane at a temperature of from 0 0 C to 100 0 C, preferably from 20°C to 65°C.
  • the resulting organic phase is treated with gaseous HCI while maintaining the reaction temperature.
  • reaction temperature is lowered, preferably to 18 - 25°C, and the introduction of gaseous hydrochloric acid is continued.
  • reaction mixture is neutralized with addition of a basic solution, for example solutions of NaHCO 3 NaCO 3 , K 2 HCO 3 , K 2 CO 3 , NaOH, KOH.
  • a basic solution for example solutions of NaHCO 3 NaCO 3 , K 2 HCO 3 , K 2 CO 3 , NaOH, KOH.
  • the phase separation subsequently takes place at elevated temperature (from about 40 to 60 0 C).
  • the organic phase (solution of the product in cyclohexane) is adjusted to a concentration of about 30 - 50% by weight by removing the solvent, and a cosolvent, for example alcohols R2-OH, esters R2COOR2, ketones R2COR2 where R2 is a C1- to C4-alkyl radical which may be linear or branched, is added.
  • a cosolvent for example alcohols R2-OH, esters R2COOR2, ketones R2COR2 where R2 is a C1- to C4-alkyl radical which may be linear or branched.
  • methanol methanol
  • the molar ratio of cyclohexane to methanol is preferably 98:2 to 80:20.
  • the crystallization of the (E)-isomer now commences. Subsequently, the temperature is lowered slowly, preferably to a temperature of from -10 to 10 0 C.
  • the resulting suspension is preferably filtered under inert gas, for example nitrogen, and the resulting crystals are washed with cyclohexane/methanol and then with methanol while cooling and dried under reduced pressure.
  • the process according to the invention affords the corresponding E-isomer in an advantageous manner in an improved isomer ratio and in high quality with at least the same rate of isomerization.
  • 116.3 g (1.3 eq) of o-methylhydroxylammonium hydrochloride solution are adjusted to pH 3.1 with 22.8 g of 50% sodium hydroxide solution and added to the reaction mixture.
  • 343.4 g of water are added and the reaction mixture is cooled to 0 0 C. Even during the addition of water, the separation of a brown-black oil is observed, which is completed by the cooling.
  • the resulting brown- black crystals are washed with 68 g of a solution of cyclohexane and methanol at 5°C (molar ratio 95:5) and three times with 34 g each time of methanol cooled to 0 0 C, in the course of which the color of the crystals changes from brown to colorless.
  • the resulting colorless crystals (content >99.5%) are dried under reduced pressure.

Landscapes

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

Abstract

L'invention porte sur un procédé perfectionné pour préparer des esters (E)-2-(2-chlorométhylphényl)-2-alcoximinoacétique représentés par la Formule (I), dans laquelle R est un radical inerte vis-à-vis de la réaction, n est 0 à 4 et R1 et R5 peuvent chacun être indépendamment des radicaux alkyle en C1-C8. Ce procédé comprend les opérations consistant à faire réagir un composé représenté par la Formule (II), dans laquelle n, R et R1 sont chacun tels que définis ci-dessus avec du chlorhydrate d'o-méthylhydroxylammonium (CH3ONH2-HCl) dans un mélange solvant à un pH de 0 à 7, qui est établi par addition d'une base inorganique, pour donner un mélange d'isomères représenté par la Formule (III), dans laquelle n, R, R1 et R5 sont chacun tels que définis ci-dessus, puis à extraire par du cyclohexane, puis à isomériser le mélange d'isomères par l'introduction d'acide chlorhydrique gazeux, la neutralisation du mélange réactionnel et la cristallisation du composé représenté par la formule (I) après addition d'un co-solvant.
PCT/EP2008/062261 2007-09-17 2008-09-15 Procédé perfectionné pour préparer des esters (e)-2-(2-chlorométhylphényl)-2-alcoximinoacétique WO2009037230A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP07018192 2007-09-17
EP07018192.0 2007-09-17

Publications (2)

Publication Number Publication Date
WO2009037230A2 true WO2009037230A2 (fr) 2009-03-26
WO2009037230A3 WO2009037230A3 (fr) 2009-07-09

Family

ID=40377284

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/062261 WO2009037230A2 (fr) 2007-09-17 2008-09-15 Procédé perfectionné pour préparer des esters (e)-2-(2-chlorométhylphényl)-2-alcoximinoacétique

Country Status (1)

Country Link
WO (1) WO2009037230A2 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3903113A (en) * 1972-05-08 1975-09-02 Janice Bradshaw Preparation of etherified hydroxyiminoacetic acids
US5449803A (en) * 1993-03-19 1995-09-12 Ube Industries, Ltd. Oxime ether compound, processes for preparing the same and fungicide containing the same
EP0782982A1 (fr) * 1996-01-03 1997-07-09 Novartis AG Procédé de préparation de dérivés de l'acide o-chloro-méthyl-phénylglyoxylique
US5856560A (en) * 1994-06-10 1999-01-05 Basf Aktiengesellschaft Preparation of a-methoxyiminocarboxylic acid methylamides and intermediates therefore
JP2002293765A (ja) * 2001-01-23 2002-10-09 Sankyo Co Ltd Ｚ−α−アルコキシイミノフェニル酢酸誘導体の製造方法
WO2008125592A1 (fr) * 2007-04-12 2008-10-23 Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg PROCÉDÉ PERFECTIONNÉ POUR LA PRÉPARATION D'ESTERS O-CHLOROMÉTHYLPHÉNYLGLYOXYLIQUES, PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION D'ESTERS (E)-2-(2-CHLOROMÉTHYLPHÉNYL)-2-ALCOXIMINOACÉTIQUES, ET NOUVEAUX INTERMÉDIAIRES POUR LEUR PR&Eacute

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3903113A (en) * 1972-05-08 1975-09-02 Janice Bradshaw Preparation of etherified hydroxyiminoacetic acids
US5449803A (en) * 1993-03-19 1995-09-12 Ube Industries, Ltd. Oxime ether compound, processes for preparing the same and fungicide containing the same
US5856560A (en) * 1994-06-10 1999-01-05 Basf Aktiengesellschaft Preparation of a-methoxyiminocarboxylic acid methylamides and intermediates therefore
EP0782982A1 (fr) * 1996-01-03 1997-07-09 Novartis AG Procédé de préparation de dérivés de l'acide o-chloro-méthyl-phénylglyoxylique
JP2002293765A (ja) * 2001-01-23 2002-10-09 Sankyo Co Ltd Ｚ−α−アルコキシイミノフェニル酢酸誘導体の製造方法
WO2008125592A1 (fr) * 2007-04-12 2008-10-23 Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg PROCÉDÉ PERFECTIONNÉ POUR LA PRÉPARATION D'ESTERS O-CHLOROMÉTHYLPHÉNYLGLYOXYLIQUES, PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION D'ESTERS (E)-2-(2-CHLOROMÉTHYLPHÉNYL)-2-ALCOXIMINOACÉTIQUES, ET NOUVEAUX INTERMÉDIAIRES POUR LEUR PR&Eacute

Also Published As

Publication number Publication date
WO2009037230A3 (fr) 2009-07-09

Similar Documents

Publication Publication Date Title
US8884033B2 (en) Process for preparing aminobenzoylbenzofuran derivatives
EP2134673A1 (fr) Procede perfectionne pour la preparation d'esters o-chloromethylphenylglyoxyliques, procede perfectionne de preparation d'esters (e)-2-(2-chloromethylphenyl)-2-alcoximinoacetiques, et nouveaux intermediaires pour leur preparation
CN106699595B (zh) 一种拉科酰胺制备方法
EP3498695B1 (fr) Procédé de synthèse d'acide 3- (difluorométhyl)-1-méthyl-1 h-pyrazole-4-carboxylique
EP2894150B1 (fr) Procédé de production d'un ester d'acide 3-fluoroalkylpyrazole-4-carboxylique substitué en position 1
WO2009037230A2 (fr) Procédé perfectionné pour préparer des esters (e)-2-(2-chlorométhylphényl)-2-alcoximinoacétique
AU737994B2 (en) Process for preparing o-(3-amino-2-hydroxy-propyl)-hydroxymic acid halides
CN112661668B (zh) 一种n-取代酰胺类化合物及其制备方法
CN101636380A (zh) 合成芳香族重氮盐的方法
CN100408554C (zh) 高纯度肼基碳酸甲酯的合成新工艺
EP0714885B1 (fr) Procédé pour la préparation d'un dérivé aminoacétamide
KR20170053644A (ko) 라코스아미드의 개선된 제조 방법 및 이의 신규한 중간산물
KR101085170B1 (ko) (ｓ)-리바스티그민의 제조방법
EP2448916B1 (fr) Production de derives d'acide trans-4-aminocyclopent-2-ene-1-carboxylique
WO2011012319A1 (fr) Procede de preparation de ƒö-amino-alcaneamides et ω-amino-alcanethioamides
CN107207435B (zh) 制备4-氰基哌啶盐酸盐的方法
EP2938595B1 (fr) Procede de synthese d'une hydrazine utile dans le traitement du virus du papillome
CN116813518A (zh) 一种奈玛特韦手性中间体的合成方法
US20110144346A1 (en) Method for producing n-phenyl-n-(4-piperidinyl) amide salts
US20070149802A1 (en) Process for preparing methyl 4-(aminomethyl)benzoate
WO2015080936A1 (fr) Procédé de production de chloridrate de n-méthylydroxylamine
EP3845518A1 (fr) Procédé de préparation de (1r,3s)-3-amino-1-cyclopentanol et de ses sels
JPH06345737A (ja) ナファゾリンまたはその塩の製造方法
PL162496B1 (pl) Sposób wytwarzania amidu kwasu N-[2-/nltrooksy/-etylo]-3-plrydynokarboksylowego
WO2013144979A1 (fr) Procédé pour la préparation d'aliskirène

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: 08804220

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08804220

Country of ref document: EP

Kind code of ref document: A2