WO2004046157A1 - Procede servant a preparer halogenure de 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl - Google Patents

Procede servant a preparer halogenure de 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl Download PDF

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Publication number
WO2004046157A1
WO2004046157A1 PCT/JP2003/014503 JP0314503W WO2004046157A1 WO 2004046157 A1 WO2004046157 A1 WO 2004046157A1 JP 0314503 W JP0314503 W JP 0314503W WO 2004046157 A1 WO2004046157 A1 WO 2004046157A1
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WO
WIPO (PCT)
Prior art keywords
bis
base
trifluoroethyl
producing
phosphine
Prior art date
Application number
PCT/JP2003/014503
Other languages
English (en)
Japanese (ja)
Inventor
Toshio Masunaga
Hitoshi Nimura
Eiji Taniyama
Original Assignee
Mitsubishi Pharma Corporation
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 Mitsubishi Pharma Corporation filed Critical Mitsubishi Pharma Corporation
Priority to JP2004553168A priority Critical patent/JPWO2004046157A1/ja
Priority to AU2003280798A priority patent/AU2003280798A1/en
Publication of WO2004046157A1 publication Critical patent/WO2004046157A1/fr

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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
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
    • 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
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
    • 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
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4075—Esters with hydroxyalkyl compounds

Definitions

  • the present invention relates to a method for producing 2- [bis (2,2,2-fluoroethyl) phosphoryl methacrylate] ethyl halide, which is described in detail below. Is a useful intermediate for the synthesis of phosphona nucleotides and the like, which are known as anti-viral agents.
  • Husband
  • ester derivatives of phosphonate nucleosides are useful as anti-HBV agents and exhibit high trans-P absorption.
  • Patent Document 1 the bis (2, 2, 2-hyfluoroethyl) ester is effective. Is one of the
  • Patent Document 1 It has been reported that the reaction can be obtained by reacting in the above-mentioned manner (Patent Document 1). Heating to 160 ° C is not possible industrially by heating with hot water at normal pressure. Equipment such as heating of the heating medium with high-pressure steam or an electric heater is required, and the reactor must also be designed to withstand the conditions. In other words, it is a factor of high cost. This reaction is accompanied by the generation of 1-chloro-2, 2, 2-tritrifluoroethane, which is a harmful substance and also an environmental pollutant, and is collected. Need to take action, and have to deal with it
  • the inventors of the present invention have conducted intensive studies in order to solve the above-mentioned problems, and as a result, they responded with a degree similar to that of Muro in 1-degree.
  • the bis (2,2,2-trifluoroethyl) phosphine of the present invention is reacted with 21-nucleotide methyl methyl ether in the presence of a base to give 2 bis (2,2,2-trifluoroethyl) phosphine.
  • the method of manufacturing [bis (2,2,2-reflection) phosphine methacrylate] halide is as follows.
  • the above base which is a method for obtaining cis ethyl halide, includes metal rim, metal hydride, hydrogenation, and hydration.
  • Metals such as porphyrium, K (LDA), etc., organic compounds such as hyphenazine, etc., total kilns, DBN, DBu, etc.
  • Examples of the base include hydrogen hydride, hydrogen hydride, and hydrogen hydride, and in particular, hydrogen hydride V is preferable.
  • the anti-J spirit is not particularly restricted, but it is -50.
  • the reaction at C ⁇ 100 ° C is especially difficult.
  • Solvents to be used are not particularly limited, but include ethyl acetate, porphyrium, tetrahydrofuran (THF), toluene, and xylene. , Acetonitrile, DMF, dimethane, ethyl acetate, acetate, methyl ethyl ketone and the like.
  • the obtained product can be separated and refined by appropriately selecting a usual separation and purification method, for example, distillation, absorption chromatogram, extraction and the like.
  • the product can be used as is.
  • the factory is manufactured by a two-story machine.

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)

Abstract

Procédé servant à préparer un halogénure de 2-[bis(2,2,2-trifluoroéthyl)phosphonylméthoxy]éthyl et consistant à effectuer la réaction de phosphite de 2-[bis(2,2,2-trifluoroéthyl) avec un éther de 2-halogénoéthyl chlorométhyl en présence d'une base. Procédé servant à préparer un ester de 2-amino-6-(4-méthoxyphénylthio)-9-[2-phosphonométhoxy)éthyl]purine bis (2,2,2-trifluoroéthyl), ce qui consiste à mettre en application ce procédé.
PCT/JP2003/014503 2002-11-15 2003-11-14 Procede servant a preparer halogenure de 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl WO2004046157A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2004553168A JPWO2004046157A1 (ja) 2002-11-15 2003-11-14 ２−［ビス（２，２，２−トリフルオロエチル）ホスホニルメトキシ］エチルハライドの製造方法
AU2003280798A AU2003280798A1 (en) 2002-11-15 2003-11-14 Process for producing 2-(bis(2,2,2-trifluoroethyl)phosphonylmethoxy)ethyl halide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002332163 2002-11-15
JP2002-332163 2002-11-15

Publications (1)

Publication Number Publication Date
WO2004046157A1 true WO2004046157A1 (fr) 2004-06-03

Family

ID=32321654

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/014503 WO2004046157A1 (fr) 2002-11-15 2003-11-14 Procede servant a preparer halogenure de 2-[bis(2,2,2-trifluoroethyl)phosphonylmethoxy]ethyl

Country Status (4)

Country Link
JP (1) JPWO2004046157A1 (fr)
AU (1) AU2003280798A1 (fr)
TW (1) TW200413399A (fr)
WO (1) WO2004046157A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105254671A (zh) * 2015-11-04 2016-01-20 天津市亨必达化学合成物有限公司 一种制备阿米福韦的方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0785208A1 (fr) * 1996-01-18 1997-07-23 Mitsubishi Chemical Corporation Composés phosphoniques de nucléotides
WO2003028737A1 (fr) * 2001-08-30 2003-04-10 Mitsubishi Pharma Corporation Agents antiviraux et procede in-vitro d'identification de candidats empechant la fixation de la polymerase a l'epsilon

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0785208A1 (fr) * 1996-01-18 1997-07-23 Mitsubishi Chemical Corporation Composés phosphoniques de nucléotides
WO2003028737A1 (fr) * 2001-08-30 2003-04-10 Mitsubishi Pharma Corporation Agents antiviraux et procede in-vitro d'identification de candidats empechant la fixation de la polymerase a l'epsilon

Also Published As

Publication number Publication date
JPWO2004046157A1 (ja) 2006-03-16
TW200413399A (en) 2004-08-01
AU2003280798A1 (en) 2004-06-15

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