WO2023049696A1 - Méthylation de 2-chloro-6-fluorophénol - Google Patents

Méthylation de 2-chloro-6-fluorophénol Download PDF

Info

Publication number
WO2023049696A1
WO2023049696A1 PCT/US2022/076700 US2022076700W WO2023049696A1 WO 2023049696 A1 WO2023049696 A1 WO 2023049696A1 US 2022076700 W US2022076700 W US 2022076700W WO 2023049696 A1 WO2023049696 A1 WO 2023049696A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
mixture
activated mixture
aqueous layer
Prior art date
Application number
PCT/US2022/076700
Other languages
English (en)
Inventor
Aman A. DESAI
Jayachandran Devaraj
Nicholas M. Irvine
Jignesh B. KANOJIYA
Jossian Oppenheimer
Smit P. PARIKH
Original Assignee
Corteva Agriscience Llc
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 Corteva Agriscience Llc filed Critical Corteva Agriscience Llc
Publication of WO2023049696A1 publication Critical patent/WO2023049696A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers

Definitions

  • the method comprises combining an organic liquid comprising a compound of formula (II) (shown below) and an aqueous solution comprising an alkali base at 20-40 °C to form an organic layer comprising chlorobenzene and an aqueous layer comprising an alkali salt of the compound of formula (II).
  • the organic layer and the aqueous layer are separated, and the aqueous layer is combined with a phase transfer catalyst and an organic solvent under activation conditions to form an activated mixture.
  • the activated mixture and a methylating agent e.g, dimethyl sulfate
  • a product mixture comprising the compound of formula (I) and by-products.
  • the method comprises combining an organic liquid comprising a compound of formula (II) (shown below) and an aqueous solution comprising an alkali base at 20-40 °C to form an organic layer comprising chlorobenzene and an aqueous layer comprising an alkali salt of the compound of formula (II).
  • the organic layer and the aqueous layer are separated, and the aqueous layer is combined with a phase transfer catalyst and an organic solvent under activation conditions to form an activated mixture.
  • the activated mixture and a methylating agent e.g, dimethyl sulfate
  • a product mixture comprising the compound of formula (I) and by-products.
  • the compound of formula (I) may be herbicidal in nature, it is particularly useful as an intermediate for production of herbicides.
  • the compound of formula (I) can be utilized to manufacture certain synthetic auxins, more particularly, certain pyridine-containing auxins.
  • the compound of formula (I) can be a building block in the manufacture of halauxifen-methyl, florpyrauxifen-benzyl, and cyanomethyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-lH-indo-l-6-yl)pyridine-2-carboxylate.
  • the compound of formula (I) can be reacted with other intermediates to form a mixture containing certain synthetic auxin herbicides such as the ones described previously, which can then be purified.
  • the compound of formula (II) is 2-chloro-6-fluorophenol (CAS 2040-90-6).
  • the amount of organic liquid to the amount of aqueous solution may be any suitable ratio of amounts, generally depending on the concentration of the reactants present in each.
  • the amount of aqueous solution will depend on the concentration of alkali base present therein, which will depend on the concentration of the compound of formula (II) present in the organic liquid.
  • any suitable alkali base may be utilized in the methods described herein. Suitable alkali bases react with the compound of formula (II) to substitute the hydrogen of the -ol group with an alkali metal ion.
  • the alkali base is selected from sodium hydroxide and potassium hydroxide. In certain embodiments of the methods provided herein, the alkali base is sodium hydroxide. In certain embodiments of the methods provided herein, the alkali base is potassium hydroxide. In certain embodiments of the methods provided herein, the alkali base is present in the aqueous solution at a concentration of from about 3 wt% to about 50 wt%.
  • the alkali base is present in the aqueous solution in an amount sufficient to provide an excess of equivalents as compared to the amount of the compound of formula (II) present in the organic liquid.
  • enough alkali base should be present to drive the compound of formula (II) to its corresponding alkali salt.
  • the amount of alkali base in the aqueous solution is from about 1.1 to about 5 equivalents as compared to the amount of the compound of formula (II) present in the organic liquid.
  • the layers are separated, and the aqueous layer containing an alkali salt of the compound of formula (II) is processed further. Separation of the layers is performed as done in the art routinely, e.g., via gravitational separation or membrane phase separation. Separation of the layers can be carried out by one skill in the art without undue experimentation.
  • activation conditions are utilized herein to describe, e.g., conditions suitable to allow for a reaction between certain molecules.
  • activation conditions are conditions such that one or more ingredients present in a mixture would react in the presence of, e.g., a methylating agent.
  • the compound of formula (II), present in the aqueous layer when combined with suitable amounts of a phase transfer catalyst and an organic solvent and at physical conditions (e.g., temperature, pressure, etc.) suitable to react with a methylating agent, should a methylating agent be introduced into the mixture, such a mixture is an “activated mixture.”
  • the activation conditions utilized to form an activated mixture include heating the combined aqueous layer, phase transfer catalyst, and organic solvent. Without wishing to be bound by theory, it is believed that activating the mixture, e.g., via heating, may provide improved chemical reaction kinetics as compared to in the absence thereof.
  • activation conditions comprise heating the mixture to a temperature of from about 60 °C to about 180 °C for from about 0.1 to about 5 hours, to form an activated mixture. In certain embodiments of the methods provided herein, activation conditions comprise heating the mixture to a temperature of from about 95 °C to about 115 °C for from about 0.5 to about 2 hours, to form an activated mixture.
  • the activated mixture is allowed to cool.
  • the term “allowed to cool” encompasses both passive (e.g., mere dissipation of heat) and active (e.g., driving cooling via refrigeration) cooling.
  • the activated mixture is allowed to cool to a temperature of from about 0 °C to about 90 °C.
  • the phase transfer catalyst may be any suitable phase transfer catalyst.
  • a suitable phase transfer catalyst is a phase transfer catalyst that allows a reaction between the alkali salt of formula (II) to react to form the compound of formula (I) at reaction conditions in the presence of dimethyl sulfate.
  • phase transfer catalysts include, but are not limited to, a crown ether, a phosphonium halide, a polyether, a phosphazenium salt, and/or a tetra- substituted ammonium halide.
  • the phase transfer catalyst is selected from tetrabutyl ammonium bromide; N-benzyl-N,N-diethylethanaminium chloride; 18-crown-6; and combinations thereof.
  • the phase transfer catalyst is tetrabutyl ammonium bromide.
  • the phase transfer catalyst is present in the activated mixture at a concentration of from about 0.001 to about 3 wt%.
  • an organic solvent is utilized in the methods provided herein to dissolve all reacting species and provide a reasonably homogeneous reacting environment.
  • any suitable organic solvent may be utilized.
  • the organic solvent is selected from toluene, xylene, cyclohexane, methyl cyclohexane, methyl ethyl ketone, heptane, pentane, and combinations thereof.
  • the organic solvent is toluene.
  • the organic solvent is present in the activated mixture at a concentration of from about 10 to about 90 wt%.
  • the activated mixture is combined with a methylating agent under reaction conditions.
  • the methylating agent can be any suitable methylating agent at a suitable concentration and purity.
  • the methylating agent can be present in a solution comprising the methylating agent, an organic solvent, and trace impurities.
  • suitable methylating agents include but are not limited to dimethyl sulfate (“DMS”), iodomethane, dimethyl carbonate, tetramethylammonium chloride, methyl trifiate, diazomethane, methyl fluorosulfonate, and combinations thereof.
  • the methylating agent is selected from DMS, iodomethane, dimethyl carbonate, tetramethylammonium chloride, methyl trifiate, diazomethane, methyl fluorosulfonate, and combinations thereof. In certain embodiments of the methods provided herein, the methylating agent is DMS.
  • the concentration of methylating agent added to the activated mixture drives the reaction of the alkali salt of the compound of formula (II) to proceed to the compound of formula (I), which is desired.
  • the combining of the activated mixture and the methylating agent is carried out at a temperature of from about 0 °C to about 90 °C.
  • the reaction conditions comprise adding the methylating agent to the activated mixture under cooling at a rate of from about 1 g/L of activated mixture per minute to about 20 g/L of activated mixture per minute.
  • the product mixture can be purified as may be necessary so as to remove a portion of the reaction by-products.
  • the methods provided herewith may include the further process step of washing, filtering (membrane or otherwise), crystallizing, separating gravitationally, and/or any other purification step known in the art and relevant to purifying the product mixture, or sub-components thereof.
  • the method is carried out as a batch process. In certain embodiments of the methods provided herewith, the method is carried out as a semi -batch (i.e., semi-continuous) process. In certain embodiments of the methods provided herewith, the method is carried out as a continuous process.
  • Each type of process e.g, batch, semi-batch, continuous
  • a batch or semi-batch process perhaps would allow for versatility in the use of capital equipment.
  • a continuous process once steady state is reached, may provide advantages in equipment sizing, efficiency, control, and reliability.
  • (C) The aspect of claim (B), wherein the purifying comprises at least one of washing, filtering, crystallizing, and separating gravitationally.
  • (D) The aspect of any one of (A)-(C), wherein the alkali base is sodium hydroxide, potassium hydroxide, or a combination thereof.
  • phase transfer catalyst is selected from a crown ether, a phosphonium halide, a polyether, a phosphazenium salt, and/or a tetrasubstituted ammonium halide.
  • phase transfer catalyst is tetrabutyl ammonium bromide.
  • reaction conditions comprise adding the dimethyl sulfate to the activated mixture under cooling and at a rate of from about 1 g/L of activated mixture/minute to about 20 g/L of activated mixture/minute.
  • (M) The aspect of any one of (A)-(L), wherein the methylating agent is selected from dimethyl sulfate (“DMS”), iodomethane, dimethyl carbonate, tetramethylammonium chloride, methyl trifiate, diazomethane, methyl fluorosulfonate, and combinations thereof.
  • DMS dimethyl sulfate
  • iodomethane dimethyl carbonate
  • tetramethylammonium chloride methyl trifiate
  • diazomethane diazomethane
  • fluorosulfonate and combinations thereof.

Landscapes

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

Abstract

L'invention concerne un procédé de formation d'un composé de formule (I) (voir ci-dessous). Le procédé comprend la combinaison d'un liquide organique comprenant un composé de formule (II) (représenté ci-après) et une solution aqueuse comprenant une base alcaline à 20-40 °C pour former une couche organique comprenant du chlorobenzène et une couche aqueuse comprenant un sel alcalin du composé de formule (II). La couche organique et la couche aqueuse sont séparées, et la couche aqueuse est combinée avec un catalyseur de transfert de phase et un solvant organique dans des conditions d'activation pour former un mélange activé. Le mélange activé et un agent de méthylation sont combinés dans des conditions de réaction pour former un mélange de produits comprenant le composé de formule (I) et des sous-produits.
PCT/US2022/076700 2021-09-21 2022-09-20 Méthylation de 2-chloro-6-fluorophénol WO2023049696A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163246336P 2021-09-21 2021-09-21
US63/246,336 2021-09-21

Publications (1)

Publication Number Publication Date
WO2023049696A1 true WO2023049696A1 (fr) 2023-03-30

Family

ID=83689960

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2022/076700 WO2023049696A1 (fr) 2021-09-21 2022-09-20 Méthylation de 2-chloro-6-fluorophénol

Country Status (1)

Country Link
WO (1) WO2023049696A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007034325A1 (fr) * 2005-09-21 2007-03-29 Pfizer Limited Derives de carboxamide en tant qu'antagonistes de recepteur muscarinique

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007034325A1 (fr) * 2005-09-21 2007-03-29 Pfizer Limited Derives de carboxamide en tant qu'antagonistes de recepteur muscarinique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAS, no. 2040-90-6

Similar Documents

Publication Publication Date Title
EP1856024A1 (fr) Procede de fabrication de biphenyls substitues
US20040106818A1 (en) Process for the preparation of cyclohexanol derivatives
WO2023049696A1 (fr) Méthylation de 2-chloro-6-fluorophénol
EP1985610A1 (fr) Procédé amélioré de production d'un dérivé de nitro-iso-urée
JP4712320B2 (ja) ２−オキソ−１−フェニル−３−オキサビシクロ［３．１．０］ヘキサンの製造方法
CN107353217B (zh) 一种邻氨基苯甲酸酯及酰胺类化合物的制备方法
JP2889231B2 (ja) 複素環系を含む芳香族化合物の製造方法
HU207718B (en) Process for producing 3,5,6-trichloropyridin-2-ol
CN113039175A (zh) 芳基磺酰基丙烯腈的制备方法
KR101856566B1 (ko) 4'-히드록시-4-비페닐카르복실산의 신규 제조 방법
JP4220619B2 (ja) 炭酸インデンの製造方法
JP4138067B2 (ja) メチン誘導体の製造方法
CN107438594B (zh) 一种用于合成环酰胺的有效的工艺
US6051714A (en) Processes for dechlorinating pyridines
JP4032861B2 (ja) β−オキソニトリル誘導体又はそのアルカリ金属塩の製法
JP4335529B2 (ja) ジヒドロピロンの連続的製造方法
JP2016169192A (ja) ７−オクテニルハライドの製造方法
WO1999044969A1 (fr) Techniques permettant d'effectuer de maniere hautement selective une o-alkylation de composes d'amide a l'aide de sels de cuivre
JP4710140B2 (ja) ピロリン誘導体の製造法
JPH04264075A (ja) チアゾリジン−２−オン誘導体の製造方法
JP2008503452A (ja) 無水アルキルホスホン酸類でのアルデヒドオキシム類から水の脱離によるニトリル類の製造方法
JP3845786B2 (ja) ジフェニルホスホリルアジドの製造方法
JP5234344B2 (ja) パラジウムヘキサフルオロアセチルアセトナートの単離方法。
JP2003238500A (ja) 含フッ素３級アミン化合物及び含フッ素４級アンモニウム塩の製造方法
WO2004035529A1 (fr) Procede de production de n-(2-amino-1,2-dicyanovinyl)formamidine

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: 22787139

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE