JPH0473437B2 - - Google Patents

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Publication number
JPH0473437B2
JPH0473437B2 JP59195642A JP19564284A JPH0473437B2 JP H0473437 B2 JPH0473437 B2 JP H0473437B2 JP 59195642 A JP59195642 A JP 59195642A JP 19564284 A JP19564284 A JP 19564284A JP H0473437 B2 JPH0473437 B2 JP H0473437B2
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JP
Japan
Prior art keywords
formula
lower alkyl
item
ester
acid
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.)
Expired - Lifetime
Application number
JP59195642A
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Japanese (ja)
Other versions
JPS6087293A (en
Inventor
Kei Sotsutashiru Jon
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.)
Bristol Myers Squibb Co
Original Assignee
Bristol Myers Squibb Co
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Filing date
Publication date
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Publication of JPS6087293A publication Critical patent/JPS6087293A/en
Publication of JPH0473437B2 publication Critical patent/JPH0473437B2/ja
Granted legal-status Critical Current

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    • 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
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/62—Isoquinoline or hydrogenated isoquinoline ring systems
    • 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
    • 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)]
    • C07F9/303—Cycloaliphatic acids
    • 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)]
    • C07F9/304—Aromatic acids (P-C aromatic linkage)
    • 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)]
    • C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
    • 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)]
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3211—Esters of acyclic saturated 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
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3223—Esters of cycloaliphatic acids
    • 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)]
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3241—Esters of arylalkanephosphinic acids
    • 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
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • 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
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems

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  • 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)

Description

【発明の詳现な説明】[Detailed description of the invention]

産業䞊の利甚分野 本発明はホスフむン酞䞭間䜓の補造法、曎に詳
しくは、䟋えばUS特蚱第4168267および4337201
号に蚘茉のホスフむン酞アンゞオテンシン倉換酵
玠抑制剀の補造に有甚な䞭間䜓の補造法に関す
る。 発明の構成ず効果 本発明によ぀お埗られる䞭間䜓は䞋蚘匏〔〕
で瀺される。 匏䞭、はたたは䜎玚アルキル、R1は䜎玚
アルキル、アリヌル、アリヌルアルキル、シクロ
アルキルたたはシクロアルキルアルキル、R2、
R3およびR4は同䞀もしくは異な぀おそれぞれ独
立しお、䜎玚アルキルたたはアリヌル、および
は䜎玚アルキル、−CO2R5R5はたたは䜎玚
アルキル、 INDUSTRIAL APPLICATION The present invention relates to a method for producing phosphinic acid intermediates, and more particularly, to US patents 4168267 and 4337201
This invention relates to a method for producing an intermediate useful for producing the phosphinate-angiotensin-converting enzyme inhibitor described in the above issue. Structure and Effects of the Invention The intermediate obtained by the present invention has the following formula []
It is indicated by. (wherein R is H or lower alkyl, R 1 is lower alkyl, aryl, arylalkyl, cycloalkyl or cycloalkylalkyl, R 2 ,
R 3 and R 4 are the same or different and each independently represents H, lower alkyl or aryl, and Z is lower alkyl, -CO 2 R 5 (R 5 is H or lower alkyl),

【匏】R6は、䜎玚アルキル、 アリヌルたたはアリヌルアルキル、−CNたたは
[Formula] (R 6 is H, lower alkyl, aryl or arylalkyl), -CN or

【匏】R7およびR8は同䞀もしくは異 な぀お、䜎玚アルキル、アリヌル、アリヌル−
䜎玚アルキル、シクロアルキルたたはシクロアル
キルアルキルで、䞔぀R7ずR8の少なくずも䞀方
は以倖、たたはR7およびR8は原子ず結合し
お、もしくは員耇玠環[Formula] (R 7 and R 8 are the same or different, H, lower alkyl, aryl, aryl-
lower alkyl, cycloalkyl or cycloalkylalkyl, and at least one of R 7 and R 8 is other than H, or R 7 and R 8 are bonded to the N atom to form a 5-, 6- or 7-membered heterocycle

【匏】を圢 成し、該耇玠環はカルボキシル基−CO2R5を
含有しあるいは含有しなくおよく、たたもしく
は員窒玠含有環は瞮合アリヌル環䟋えばプ
ニル環を含有しお窒玠含有環[Formula], the heterocycle may or may not contain a carboxyl group (-CO 2 R 5 ), and the 5- or 6-membered nitrogen-containing ring contains a fused aryl ring (e.g., a phenyl ring). nitrogen-containing ring

【匏】が その瞮合アリヌル環ず合しむンドヌルたたはテト
ラヒドロむ゜キノリン系、䟋えば [Formula] is combined with its fused aryl ring to form an indole or tetrahydroisoquinoline system, e.g.

【匏】たたは[expression] or

【匏】 n′はたたは を圢成し、あるいは圢成しなくおよいである〕 䞊蚘匏〔〕のホスフむン酞䞭間䜓を補造する
本発明の方法は、匏 〔匏䞭、はたたは䜎玚アルキル、およびR1
は䜎玚アルキル、アリヌル、アリヌルアルキル、
シクロアルキルたたはシクロアルキルアルキルで
ある〕 の亜ホスホン酞たたはその゚ステルを、匏 〔匏䞭、R2、R3およびR4は同䞀もしくは異な぀
おそれぞれ、䜎玚アルキルたたはアリヌル、お
よびは䜎玚アルキル、−CO2R5R5はたたは
䜎玚アルキル、[Formula] (n' is 0 or 1) or not formed]] The method of the present invention for producing the phosphinic acid intermediate of the above formula [] has the formula: [wherein R is H or lower alkyl, and R 1
is lower alkyl, aryl, arylalkyl,
cycloalkyl or cycloalkylalkyl] or its ester with the formula: [In the formula, R 2 , R 3 and R 4 are the same or different and each is H, lower alkyl or aryl, and Z is lower alkyl, -CO 2 R 5 (R 5 is H or lower alkyl),

【匏】R6は、䜎玚アル キル、アリヌルたたはアリヌルアルキル、−CN
たたは[Formula] (R 6 is H, lower alkyl, aryl or arylalkyl), -CN
or

【匏】R7およびR8は同䞀もしくは異 な぀お氎玠、䜎玚アルキル、アリヌル、アリヌル
−䜎玚アルキル、シクロアルキルたたはシクロア
ルキルアルキルで、䞔぀R7ずR8の少なくずも䞀
方は氎玠以倖、たたはR7およびR8は窒玠原子ず
結合しお、もしくは員耇玠環
[Formula] (R 7 and R 8 are the same or different and are hydrogen, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl, or cycloalkylalkyl, and at least one of R 7 and R 8 is other than hydrogen, or R 7 and R 8 is bonded to the nitrogen atom to form a 5-, 6-, or 7-membered heterocyclic ring

【匏】を圢成し、該環はカルボキシル基 −CO2R5を含有しあるいは含有しなくおよく
たたもしくは員含有環は瞮合アリヌル環
䟋えばプニル環を含有なお、かかる瞮合
系の䟋は䞊蚘の通りしあるいは含有しなくおよ
いである〕 の共圹化合物ず、シリル化剀および䞍掻性有機溶
媒の存圚䞋で反応させおホスフむン酞䞭間䜓
〔〕を圢成する工皋を包含し、該䞭間䜓を反応
混合物から分離し、䟋えばU.S.特蚱第4168267お
よび4337201号に蚘茉のホスフむン酞アンゞオテ
ンシン倉換酵玠抑制剀の補造に甚いるこずができ
る。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「アリヌル」ずは、プニ
ルたたは眮換プニル眮換基ずしおハロゲン、
アルキル、アルコキシ、アルキルチオ、ヒドロキ
シ、アルカノむル、ニトロ、アミノ、ゞアルキル
アミノたたはトリフルオロメチルを指称する。
プニルおよびモノ眮換プニルが奜たしく、フ
゚ニルが最も奜たしい。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「アルキル」たたは「䜎玚
アルキル」ずは、炭玠数〜10の基を指称する。
炭玠数〜のアルキル基が奜たしい。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「シクロアルキル」ずは、
炭玠数〜の基を指称する。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「アルコキシ」たたは「ア
ルキルチオ」ずは、炭玠数〜の基を指称す
る。炭玠数〜のアルコキシたたはアルキルチ
オ基が奜たしい。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「アリヌルアルキル」たた
は「シクロアルキルアルキル」ずは、アリヌルた
たはシクロアルキル眮換基を有する䞊述のアルキ
ル基を指称する。 本明现曞を通じそれ自䜓たたはより倧なる基の
䞀郚ずしお甚いる語句「アルカノむル」ずは、䞊
述のアルキル基がカルボニル基The ring may or may not contain a carboxyl group (-CO 2 R 5 ), and the 5- or 6-membered N-containing ring may contain a fused aryl ring (e.g., a phenyl ring). An example of such a condensation system is the conjugated compound (which may or may not contain) as described above) in the presence of a silylating agent and an inert organic solvent to form the phosphinic acid intermediate. The intermediate can be separated from the reaction mixture and used, for example, in the preparation of phosphinate angiotensin converting enzyme inhibitors as described in US Pat. Nos. 4,168,267 and 4,337,201. The term "aryl," as used herein by itself or as part of a larger group, means phenyl or substituted phenyl (halogen as a substituent,
alkyl, alkoxy, alkylthio, hydroxy, alkanoyl, nitro, amino, dialkylamino or trifluoromethyl).
Phenyl and monosubstituted phenyl are preferred, with phenyl being most preferred. The term "alkyl" or "lower alkyl," as used herein by itself or as part of a larger group, refers to groups having 1 to 10 carbon atoms.
An alkyl group having 1 to 4 carbon atoms is preferred. The term "cycloalkyl," as used herein by itself or as part of a larger group, means
Refers to a group having 3 to 7 carbon atoms. The terms "alkoxy" or "alkylthio," as used herein by themselves or as part of a larger group, refer to groups having from 1 to 8 carbon atoms. An alkoxy or alkylthio group having 1 to 3 carbon atoms is preferred. The terms "arylalkyl" or "cycloalkylalkyl" as used herein by themselves or as part of a larger group refer to an alkyl group as described above having an aryl or cycloalkyl substituent. The term "alkanoyl," as used by itself or as part of a larger group throughout this specification, means that an alkyl group as described above is a carbonyl group.

【匏】に結合 したものを指称する。 本発明方法を実斜しお匏〔〕の化合物を補造
するに際し、出発物質の亜ホスホン酞たたはその
゚ステル〔〕をシリル化剀の存圚䞋、玄℃〜
環流枩床玄120℃、奜たしくは玄10〜50℃の範
囲内の枩床で共圹化合物ず反応させる。反応は、
䞍掻性有機溶媒䟋えばクロロホルム、アセトニ
トリル、ゞクロロメタン、゚チル゚ヌテル、テト
ラヒドロフランたたはゞオキサンの存圚䞋、お
よび必芁に応じお有機塩基䟋えばトリ゚チルア
ミン、ピリゞンたたは−ゞメチルアミン
の存圚䞋玄〜10時間、奜たしくは玄〜時間
で行う。 本発明の実斜に際し出発物質ずしお甚いる亜ホ
スホン酞たたはその゚ステル〔〕の具䜓䟋ずし
おは、[Formula] indicates what is combined with [Formula]. When carrying out the method of the present invention to produce the compound of formula [], the starting material phosphorous acid or its ester [] is heated at about 0°C to
React with the conjugated compound at reflux temperature (approximately 120°C), preferably at a temperature within the range of approximately 10-50°C. The reaction is
in the presence of an inert organic solvent (e.g. chloroform, acetonitrile, dichloromethane, ethyl ether, tetrahydrofuran or dioxane) and optionally an organic base (e.g. triethylamine, pyridine or N,N-dimethylamine).
for about 2 to 10 hours, preferably for about 5 to 8 hours. Specific examples of phosphonic acid or its ester used as a starting material in carrying out the present invention include:

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】たたは[expression] or

【匏】 が包含されるが、これらに限定されるものでな
い。It includes, but is not limited to, the formula:

【匏】たたはその゚ステルが奜 たしい。 本発明の実斜に際し甚いる共圹化合物〔〕の
具䜓䟋ずしおは、 H2CH  CN、C6H5 CHCOOH、CH2CHCO2H、 CH2CHCOOCH3、C6H5−CH2 CHCOC6H5、[Formula] or its ester is preferred. Specific examples of the conjugated compounds [] used in carrying out the present invention include H 2 C= H C CN, H(C 6 H 5 )C=CHCOOH, CH 2 =CHCO 2 H, CH 2 =CHCOOCH 3 , H( C 6 H 5 −CH 2 )C = CHCOC 6 H 5 ,

【匏】【formula】

【匏】【formula】

【匏】C6H5CHCN、[Formula] H(C 6 H 5 )C=CHCN,

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】【formula】

【匏】たたは[expression] or

【匏】が包含されるが、 これらに限定されるものでない。H2CCHCN
が奜たしい。 本発明方法の実斜に際し、䜿甚に奜適なシリル
化剀の具䜓䟋ずしおは、トリメチルシリルクロリ
ドおよびトリ゚チルアミン、モノシリルアセトア
ミド、ビスシリルアセトアミド、モノシリルトリ
フルオロアセトアミドおよびビスシリルトリフル
オロアセトアミドが包含されるが、これらに限定
されるものでない。 䞊述の本発明方法の実斜に際し、共圹化合物
〔〕およびシリル化剀に察する亜ホスホン酞た
たはその゚ステル〔〕の䜿甚量は、出発亜ホス
ホン酞たたはその゚ステル〔〕䞭の眮換基ず
共圹化合物〔〕䞭の眮換基に䟝存する。即
ち、が䜎玚アルキルおよびが−CO2・アルキ
ル、䜎玚アルキル、[Formula] is included, but not limited to. H2C CHCN
is preferred. Specific examples of silylating agents suitable for use in carrying out the process of the invention include trimethylsilyl chloride and triethylamine, monosilylacetamide, bissilylacetamide, monosilyltrifluoroacetamide and bissilyltrifluoroacetamide. It is not limited to. In carrying out the above-described method of the present invention, the amount of phosphorous acid or its ester [] to be used relative to the conjugated compound [] and the silylating agent is determined based on the R substituent in the starting phosphonic acid or its ester [] and the conjugated compound [] depending on the Z substituent in. That is, R is lower alkyl and Z is -CO 2 ·alkyl, lower alkyl,

【匏】−CNたたは[Formula]-CN or

【匏】である堎合、亜ホスホン酞たたは その゚ステル〔〕ず共圹化合物〔〕ずのモル
比を玄0.5〜10の範囲内で蚭定し、たた
亜ホスホン酞たたはその゚ステル〔〕ずシリル
化剀ずのモル比を玄0.5〜10の範囲内で
蚭定する。 亜ホスホン酞たたはその゚ステル〔〕のが
で、共圹化合物〔〕のが䜎玚アルキル、−
CO2R5R5は䜎玚アルキル、[Formula], the molar ratio of phosphorous acid or its ester [] and the conjugated compound [] is set within the range of about 0.5:1 to 10:1, and the phosphorous acid or its ester [] The molar ratio with the silylating agent is set within the range of about 0.5:1 to 1:10. R of phosphorous acid or its ester [] is H, Z of the conjugated compound [] is lower alkyl, -
CO 2 R 5 (R 5 is lower alkyl),

【匏】−CN たたは[Formula]-CN or

【匏】である堎合、亜ホスホン酞 たたはその゚ステル〔〕ず共圹化合物〔〕ず
のモル比を玄0.5〜10の範囲内で蚭定し、
たた亜ホスホン酞たたはその゚ステル〔〕ずシ
リル化剀ずのモル比を玄0.2〜10の範囲
内で蚭定する。 亜ホスホン酞出発物質を甚いる、即ち匏〔〕
䞭のがで、共圹化合物〔〕䞭のが−
CO2Hたたは[Formula], the molar ratio of phosphorous acid or its ester [] and conjugated compound [] is set within the range of about 0.5:1 to 10:1,
Further, the molar ratio of the phosphorous acid or its ester [ ] and the silylating agent is set within the range of about 0.2:1 to 1:10. Using a phosphonous acid starting material, i.e. formula []
R in the compound is H, and Z in the conjugated compound [ ] is -
CO2H or

【匏】である堎合、 亜ホスホン酞〔〕ず共圹化合物〔〕ずのモル
比を玄0.5〜10の範囲内で蚭定し、亜ホ
スホン酞〔〕ずシリル化剀ずのモル比を玄
0.1〜15の範囲内で蚭定する。 匏〔〕の亜ホスホン酞゚ステル即ち、が
アルキルを甚い、䜿甚する共圹化合物が酞、即
ち匏〔〕䞭のが−CO2Hたたは[Formula], the molar ratio of phosphonic acid [] and conjugated compound [] is set within the range of about 0.5:1 to 10:1, and the molar ratio of phosphonic acid [] and silylating agent is set within the range of about 0.5:1 to 10:1. Approximately
Set within the range of 0.1:1 to 1:15. A phosphonite of the formula [] (i.e., R is alkyl) is used, and the conjugate compound used is an acid, that is, Z in the formula [] is -CO 2 H or

【匏】である堎合、亜ホスホン酞 ゚ステル〔〕ず共圹化合物ずのモル比を玄
0.5〜10の範囲内で蚭定し、亜ホスホン
酞゚ステル〔〕ずシリル化剀ずのモル比を玄
0.1〜15の範囲内で蚭定する。 匏〔〕の亜ホスホン酞゚ステル即ち、が
アルキルを甚い、䜿甚する共圹化合物が酞、即
ち匏〔〕䞭のが−CO2Hたたは[Formula], the molar ratio of the phosphonite [] and the conjugated compound is approximately
Set within the range of 0.5:1 to 10:1, and keep the molar ratio of phosphonite [] and silylating agent to approx.
Set within the range of 0.1:1 to 1:15. A phosphonite of the formula [] (i.e., R is alkyl) is used, and the conjugate compound used is an acid, that is, Z in the formula [] is -CO 2 H or

【匏】である堎合、亜ホスホン酞 ゚ステル〔〕ず共圹化合物ずのモル比を玄
0.5〜10の範囲内で蚭定し、亜ホスホン
酞゚ステル〔〕ずシリル化剀ずのモル比を玄
0.2〜10の範囲内で蚭定する。 ホスフむン酞䞭間䜓〔〕を゚ステルの圢状で
埗る堎合、かかる゚ステルを通垞の方法で䟋えば
該゚ステルを氎酞化ナトリりムず反応させ、遊離
酞に倉換するこずができる。 が䜎玚アルキルである匏〔〕の゚ステル
は、がであるカルボン酞化合物から通垞の゚
ステル化法で、䟋えばゞアゟメタンによる゚ステ
ル化たたは沃化メチルたたは他のアルキルハラ
むドおよび塩基䟋えばトリ゚チルアミン、炭
酞カリりム等ずの反応によ぀お埗るこずができ
る。 次に挙げる実斜䟋は本発明の奜たしい具䜓䟋で
ある。他に特別指瀺がなければ、枩床単䜍は℃で
衚瀺する。 実斜䟋  −〔ヒドロキシ−−プニルブチルホス
フむニル〕プロピオニトリルの補造− クロロホルム15ml䞭の−プニルブチル
亜ホスホン酞0.44、0.0022モルの溶液に、
トリ゚チルアミン0.68ml、トリメチルシリル
クロリド0.61mlおよびアクリロニトリル
0.17mlを加え、反応混合物を宀枩で18時間撹
拌する。混合物を粉砕氷15を含む10mlの10
HClに泚ぐ。これを分液挏斗にお振盪し、クロ
ロホルム局を蒞発し、氎性局をクロロホルム20ml
で回抜出する。集めた有機盞を氎で掗い、無氎
硫酞ナトリりム䞊で也燥し、有機溶媒を回転蒞発
噚rotavapにお陀去し、暙蚘化合物を高結晶
固䜓で埗る収率99。 実斜䟋  −〔ヒドロキシ−プニルブチルホス
フむニル〕プロピオン酞の補造− アクリロニトリルの代わりにアクリル酞を甚い
る以倖は、実斜䟋ず同様にしお暙蚘化合物を埗
る。 実斜䟋  −〔ヒドロキシプニルホスフむニル〕−
−プニルプロピオン酞メチル゚ステルの補
造− −プニルブチル亜ホスホン酞の代わりにフ
゚ニル亜ホスホン酞を甚い、アクリロニトリルの
代わりにメチルシンナメヌトを甚いる以倖は、実
斜䟋ず同様にしお暙蚘化合物を埗る。 実斜䟋  −〔゚トキシプロピルホスフむニル〕−
−プニル−−メチル−プロピオン酞の補
造− −プニルブチル亜ホスホン酞の代わりにプ
ロピル亜ホスホン酞゚チル゚ステルを甚い、アク
リロニトリルの代わりに−メチル−−プニ
ルアクリル酞を甚いる以倖は、実斜䟋ず同様に
しお暙蚘化合物を埗る。 実斜䟋  −〔゚トキシシクロヘキシルホスフむニ
ル〕−−メチル−−プニル−プロピオン
酞メチル゚ステルの補造− −プニルブチル亜ホスホン酞の代わりにシ
クロヘキシル亜ホスホン酞を甚い、アクリロニト
リルの代わりに−プニル−−メチル−アク
リル酞メチル゚ステルを甚いる以倖は、実斜䟋
ず同様にしお暙蚘化合物を埗る。 実斜䟋  −〔ヒドロキシシクロペンチルホスフむニ
ル〕−−ゞ゚チルプロピオン酞メチル゚
ステルの補造− −プニルブチル亜ホスホン酞の代わりにシ
クロペンチル亜ホスホン酞を甚い、アクリロニト
リルの代わりに−ゞ゚チル−アクリル酞メ
チル゚ステルを甚いる以倖は、実斜䟋ず同様に
しお暙蚘化合物を埗る。 実斜䟋  −〔ヒドロキシプニルホスフむニル〕−
−メチル−プロピオン酞メチル゚ステルの補
造− −プニルブチル亜ホスホン酞の代わりにフ
゚ニル亜ホスホン酞を甚い、アクリロニトリルの
代わりに−メチル−アクリル酞メチル゚ステル
を甚いる以倖は、実斜䟋ず同様にしお暙蚘化合
物を埗る。 実斜䟋  −〔ヒドロキシベンゞルホスフむニル〕プ
ロピオン酞ベンゞル゚ステルの補造− −プニルブチル亜ホスホン酞の代わりにベ
ンゞル亜ホスホン酞を甚い、アクリロニトリルの
代わりにアクリル酞ベンゞルを甚いる以倖は、実
斜䟋ず同様にしお暙蚘化合物を埗る。 実斜䟋  −〔ヒドロキシプロピルホスフむニル〕−
−ゞメチルプロピオノニトリルの補造
− −プニルブチル亜ホスホン酞の代わりにプ
ロピル亜ホスホン酞を甚い、アクリロニトリルの
代わりに−ゞメチルアクリロニトリルを甚
いる以倖は、実斜䟋ず同様にしお暙蚘化合物を
埗る。 実斜䟋 10 −〔メトキシブチルホスフむニル〕−−
゚チル−プロピオン酞ベンゞル゚ステルの補
造− −プニルブチル亜ホスホン酞の代わりにブ
チル亜ホスホン酞メチル゚ステルを甚い、アクリ
ロニトリルの代わりに−゚チル−アクリル酞ベ
ンゞル゚ステルを甚いる以倖は、実斜䟋ず同様
にしお暙蚘化合物を埗る。 実斜䟋 11 −〔ヒドロキシ−プニルブチルホス
フむニル〕プロピオン酞−ゞメチルアミ
ドの補造− アクリロニトリルの代わりに−ゞメチル
アクリルアミドを甚いる以倖は、実斜䟋ず同様
にしお暙蚘化合物を埗る。 実斜䟋 12 −〔ヒドロキシ−プニルブチルホス
フむニル〕プロピオニル−−プロリン・メチ
ル゚ステルの補造− アクリロニトリルの代わりに−アクリロむル
−−プロリン・メチル゚ステルを甚いる以倖
は、実斜䟋ず同様にしお暙蚘化合物を埗る。 実斜䟋 13 −〔−〔ヒドロキシ−プニルブチル
ホスフむニル〕プロピオニル〕むンドリン−
−カルボン酞の補造− アクリロニトリルの代わりに−アクリロむル
むンドリン−−カルボン酞を甚いる以倖は、実
斜䟋ず同様にしお暙蚘化合物を埗る。 実斜䟋 14 −〔−〔ヒドロキシ−−プニルブチル
ホスフむニル〕プロピオニル〕−
−テトラヒドロむ゜キノリン−−カルボン
酞の補造− アクリロニトリルの代わりに−アクリロむル
−−テトラヒドロむ゜キノリン−
−カルボン酞を甚いる以倖は、実斜䟋ず同様
にしお暙蚘化合物を埗る。 実斜䟋 15 −〔−〔ヒドロキシ−−プニルブチル
ホスフむニル〕プロピオニル〕−
−テトラヒドロむ゜キノリンの補造− アクリロニトリルの代わりに−アクリロむル
−−テトラヒドロむ゜キノリンを
甚いる以倖は、実斜䟋ず同様にしお暙蚘化合物
を埗る。 実斜䟋 16 −〔−〔ヒドロキシ−−プニルブチル
ホスフむニル〕プロピオニル〕むンドリンの補
造− アクリロニトリルの代わりに−アクリロむル
むンドリンを甚いる以倖は、実斜䟋ず同様にし
お暙蚘化合物を埗る。 実斜䟋 17 −〔−〔ヒドロキシ−−プニルブチル
ホスフむニル〕−−メチルプロピオニル〕−
−テトラヒドロむ゜キノリン−
−カルボン酞の補造− アクリロニトリルの代わりに−クロトノむル
−−テトラヒドロむ゜キノリン−
−カルボン酞を甚いる以倖は、実斜䟋ず同様
にしお暙蚘化合物を埗る。[Formula], the molar ratio of the phosphonite [] and the conjugated compound is approximately
Set within the range of 0.5:1 to 10:1, and keep the molar ratio of phosphonite [] and silylating agent to approx.
Set within the range of 0.2:1 to 1:10. When the phosphinic acid intermediate [ ] is obtained in the form of an ester, such an ester can be converted into the free acid in a conventional manner, for example by reacting the ester with sodium hydroxide. Esters of formula [] in which R is lower alkyl can be prepared from carboxylic acid compounds in which R is H by conventional esterification methods, for example by esterification with diazomethane or by esterification with methyl iodide (or other alkyl halide) and a base (for example triethylamine). , potassium carbonate, etc.). The following examples are preferred embodiments of the invention. Unless otherwise specified, temperature units are expressed in °C. Example 1 Preparation of 3-[hydroxy-(4-phenylbutyl)phosphinyl]propionitrile: - To a solution of 4-phenylbutylphosphonic acid (0.44 g, 0.0022 mol) in chloroform (15 ml),
Triethylamine (0.68ml), trimethylsilyl chloride (0.61ml) and acrylonitrile (0.17ml) are added and the reaction mixture is stirred at room temperature for 18 hours. Mix 10 ml of crushed ice (15 g)
Pour into %HCl. Shake this in a separatory funnel, evaporate the chloroform layer, and remove the aqueous layer with 20 ml of chloroform.
Extract once. The combined organic phases are washed with water, dried over anhydrous sodium sulphate and the organic solvent is removed on a rotavap to give the title compound as a highly crystalline solid (99% yield). Example 2 Preparation of 3-[hydroxy(4-phenylbutyl)phosphinyl]propionic acid: - The title compound is obtained in the same manner as in Example 1, except that acrylic acid is used instead of acrylonitrile. Example 3 3-[Hydroxy(phenyl)phosphinyl]-
Production of 3-phenylpropionic acid methyl ester: - The title compound was prepared in the same manner as in Example 1, except that phenylphosphonic acid was used in place of 4-phenylbutylphosphonic acid and methyl cinnamate was used in place of acrylonitrile. obtain. Example 4 3-[ethoxy(propylphosphinyl)]-3
- Preparation of phenyl-2-methyl-propionic acid: - except that propylphosphonic acid ethyl ester is used instead of 4-phenylbutylphosphonite and 2-methyl-3-phenyl acrylic acid is used instead of acrylonitrile. The title compound is obtained in the same manner as in Example 1. Example 5 Preparation of 3-[ethoxy(cyclohexylphosphinyl)]-3-methyl-2-phenyl-propionic acid methyl ester: - Using cyclohexylphosphonite in place of 4-phenylbutylphosphonite and in place of acrylonitrile. Example 1 except that 2-phenyl-3-methyl-acrylic acid methyl ester was used for
The title compound is obtained in the same manner as above. Example 6 Preparation of 3-[hydroxy(cyclopentylphosphinyl)]-3,3-diethylpropionic acid methyl ester: - Using cyclopentylphosphonite in place of 4-phenylbutylphosphonite and 3,3 in place of acrylonitrile. The title compound is obtained in the same manner as in Example 1, except that 3-diethyl-acrylic acid methyl ester is used. Example 7 3-[Hydroxy(phenylphosphinyl)]-
Preparation of 3-methyl-propionic acid methyl ester: - Same as Example 1, except that phenylphosphonic acid is used instead of 4-phenylbutylphosphonic acid and 3-methyl-acrylic acid methyl ester is used instead of acrylonitrile. to obtain the title compound. Example 8 Preparation of benzyl 3-[hydroxy(benzylphosphinyl)]propionate ester: - Using benzylphosphonite instead of 4-phenylbutylphosphonite and benzyl acrylate instead of acrylonitrile. The title compound is obtained in the same manner as in Example 1. Example 9 3-[Hydroxy(propylphosphinyl)]-
Production of 3,3-dimethylpropiononitrile:
- The title compound is obtained in the same manner as in Example 1, except that propylphosphonic acid is used instead of 4-phenylbutylphosphonic acid and 3,3-dimethylacrylonitrile is used instead of acrylonitrile. Example 10 3-[methoxy(butylphosphinyl)]-3-
Preparation of ethyl-propionate benzyl ester: - Same as Example 1 except that butyl methyl phosphonite is used instead of 4-phenylbutyl phosphonite and 3-ethyl-acrylic acid benzyl ester is used instead of acrylonitrile. to obtain the title compound. Example 11 Preparation of 3-[hydroxy(4-phenylbutyl)phosphinyl]propionic acid N,N-dimethylamide: - The title compound was prepared in the same manner as in Example 1, except that N,N-dimethylacrylamide was used in place of acrylonitrile. get. Example 12 Production of 3-[hydroxy(4-phenylbutyl)phosphinyl]propionyl-L-proline methyl ester: - Same as Example 1 except that N-acryloyl-L-proline methyl ester is used instead of acrylonitrile. to obtain the title compound. Example 13 1-[3-[hydroxy(4-phenylbutyl)]
Phosphinyl]propionyl]indoline-3
- Production of carboxylic acid: - The title compound is obtained in the same manner as in Example 1, except that 1-acryloyl indoline-3-carboxylic acid is used instead of acrylonitrile. Example 14 2-[3-[hydroxy-(4-phenylbutyl)]
Phosphinyl]propionyl]-1,2,3,
Preparation of 4-tetrahydroisoquinoline-1-carboxylic acid: - 2-acryloyl-1,2,3,4-tetrahydroisoquinoline instead of acrylonitrile -
The title compound is obtained in the same manner as in Example 1 except that 1-carboxylic acid is used. Example 15 2-[3-[hydroxy-(4-phenylbutyl)]
Phosphinyl]propionyl]-1,2,3,
Preparation of 4-tetrahydroisoquinoline: - The title compound is obtained in the same manner as in Example 1, except that 2-acryloyl-1,2,3,4-tetrahydroisoquinoline is used instead of acrylonitrile. Example 16 1-[3-[hydroxy-(4-phenylbutyl)]
Preparation of phosphinyl]propionyl]indoline: - The title compound is obtained in the same manner as in Example 1, except that 1-acryloylindoline is used instead of acrylonitrile. Example 17 2-[3-[hydroxy-(4-phenylbutyl)]
Phosphinyl]-3-methylpropionyl]-
1,2,3,4-tetrahydroisoquinoline-
Preparation of 1-carboxylic acid: - 2-crotonoyl-1,2,3,4-tetrahydroisoquinoline- instead of acrylonitrile
The title compound is obtained in the same manner as in Example 1 except that 1-carboxylic acid is used.

Claims (1)

【特蚱請求の範囲】  匏、 〔匏䞭、はたたは䜎玚アルキル、およびR1
は䜎玚アルキル、アリヌル、アリヌルアルキル、
シクロアルキルたたはシクロアルキルアルキルで
ある〕 で瀺される亜ホスホン酞たたはその゚ステルを、 匏、 〔匏䞭、R2、R3およびR4は同䞀もしくは異な぀
おそれぞれ独立しお、䜎玚アルキルたたはアリ
ヌル、および は䜎玚アルキル、−CO2R5R5はたたは䜎
玚アルキル、【匏】R6は、䜎玚アルキ ル、アリヌルたたはアリヌルアルキル、−CNた
たは【匏】R7およびR8は同䞀もしく は異な぀お、䜎玚アルキル、アリヌル、アリヌ
ル−䜎玚アルキル、シクロアルキルおよびシクロ
アルキルアルキルからなる矀から遞ばれ、䞔぀
R7ずR8の少なくずも䞀方は以倖、たたはR7お
よびR8は原子ず結合しお、もしくは員
耇玠環【匏】を圢成し、該耇玠環は− COOR5基を含有しあるいは含有しなくおよく、
たたもしくは員含有環はアリヌル環に瞮合
しあるいは瞮合しなくおよいである〕 で瀺される共圹化合物ず、シリル化剀および䞍掻
性有機溶媒の存圚䞋で反応させ、匏、 〔匏䞭、、R1、R2、R3、R4およびは前蚘ず
同意矩〕 で瀺されるホスフむン酞䞭間䜓を圢成するこずを
特城ずするホスフむン酞䞭間䜓の補造法。  反応を塩基の存圚䞋で行う前蚘第項蚘茉の
方法。  塩基がトリ゚チルアミン、ピリゞンたたは
−ゞメチルアミンである前蚘第項蚘茉の
方法。  䞍掻性有機溶媒がクロロホルム、アセトニト
リル、ゞクロロメタン、゚チル゚ヌテル、テトラ
ヒドロフランたたはゞオキサンである前蚘第項
蚘茉の方法。  シリル化剀がトリメチルシリルクロリドおよ
びトリ゚チルアミン、モノシリルアセトアミド、
ビスシリルアセトアミド、モノシリルトリフルオ
ロアセトアミドもしくはビスシリルトリフルオロ
アセトアミドである前蚘第項蚘茉の方法。  シリル化剀がトリメチルシリルクロリドおよ
びトリ゚チルアミンである前蚘第項蚘茉の方
法。  亜ホスホン酞たたはその゚ステルにおける
が䜎玚アルキルで、共圹化合物におけるが゚ス
テル−CO2・䜎玚アルキル、䜎玚アルキル、
【匏】【匏】たたは−CNである 前蚘第項蚘茉の方法。  亜ホスホン酞゚ステルを共圹化合物ずのモル
比が玄0.5〜10の範囲内で甚い、䞔぀亜
ホスホン酞゚ステルをシリル化剀ずのモル比が玄
0.5〜10の範囲内で甚いる前蚘第項蚘
茉の方法。  亜ホスホン酞たたはその゚ステルにおける
がで、共圹化合物におけるが゚ステル−
CO2・䜎玚アルキル、䜎玚アルキル、
【匏】【匏】たたは−CNである 前蚘第項蚘茉の方法。  亜ホスホン酞を共圹化合物ずのモル比が玄
0.5〜10の範囲内で甚い、䞔぀亜ホスホ
ン酞をシリル化剀ずのモル比が玄0.2〜
10の範囲内で甚いる前蚘第項蚘茉の方法。  亜ホスホン酞たたはその゚ステルのが䜎
玚アルキルで、共圹化合物におけるが−
COOHたたは【匏】である前蚘 第項蚘茉の方法。  亜ホスホン酞゚ステルを共圹化合物ずのモ
ル比が玄0.5〜10の範囲内で甚い、䞔぀
亜ホスホン酞゚ステルをシリル化剀ずのモル比が
箄0.2〜10の範囲内で甚いる前蚘第
項蚘茉の方法。  亜ホスホン酞たたはその゚ステルにおける
がで、共圹化合物におけるが−COOHた
たは【匏】である前蚘第項蚘 茉の方法。  亜ホスホン酞を共圹化合物ずのモル比が玄
0.5〜10の範囲内で甚い、䞔぀亜ホスホ
ン酞をシリル化剀ずのモル比が玄0.1〜
15の範囲内で甚いる前蚘第項蚘茉の方法。  亜ホスホン酞たたはその゚ステルず共圹化
合物の反応を、〜120℃の範囲内の枩床で行う
前蚘第項蚘茉の方法。  亜ホスホン酞が
【匏】共圹化合物が H2CCHCNで、シリル化剀がCH33SiClおよ
びC2H53Nである前蚘第項蚘茉の方法。[Claims] 1 formula, [wherein R is H or lower alkyl, and R 1
is lower alkyl, aryl, arylalkyl,
cycloalkyl or cycloalkylalkyl] Phosphonous acid or its ester represented by the formula, [In the formula, R 2 , R 3 and R 4 are the same or different and each independently represents H, lower alkyl or aryl, and Z is lower alkyl, -CO 2 R 5 (R 5 is H or lower alkyl), [ Formula] (R 6 is H, lower alkyl, aryl or arylalkyl), -CN or [Formula] (R 7 and R 8 are the same or different H, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl and cyclo selected from the group consisting of alkylalkyl, and
At least one of R 7 and R 8 is other than H, or R 7 and R 8 are combined with the N atom to form a 5-, 6-, or 7-membered heterocycle [Formula], and the heterocycle contains -COOR 5 groups. It may not contain or contain
In addition, the 5- or 6-membered N-containing ring may or may not be fused to the aryl ring)] in the presence of a silylating agent and an inert organic solvent. [In the formula, R, R 1 , R 2 , R 3 , R 4 and Z have the same meanings as above] A method for producing a phosphinic acid intermediate, which comprises forming a phosphinic acid intermediate represented by the following formula. 2. The method according to item 1 above, wherein the reaction is carried out in the presence of a base. 3. The method according to item 2 above, wherein the base is triethylamine, pyridine or N,N-dimethylamine. 4. The method according to item 1 above, wherein the inert organic solvent is chloroform, acetonitrile, dichloromethane, ethyl ether, tetrahydrofuran or dioxane. 5 The silylating agent is trimethylsilyl chloride and triethylamine, monosilylacetamide,
2. The method according to item 1, which is bissilylacetamide, monosilyltrifluoroacetamide or bissilyltrifluoroacetamide. 6. The method according to item 1 above, wherein the silylating agent is trimethylsilyl chloride and triethylamine. 7 R in phosphonic acid or its ester
is lower alkyl, and Z in the conjugated compound is ester (-CO 2 /lower alkyl), lower alkyl,
The method according to item 1 above, wherein [Formula] [Formula] or -CN. 8 The phosphonite is used in a molar ratio of about 0.5:1 to 10:1 with the conjugated compound, and the molar ratio of the phosphonite with the silylating agent is about 0.5:1 to 10:1.
The method according to item 7 above, wherein the ratio is within the range of 0.5:1 to 1:10. 9 R in phosphonic acid or its ester
is H, and Z in the conjugated compound is ester (-
CO2・lower alkyl), lower alkyl,
The method according to item 1 above, wherein [Formula] [Formula] or -CN. 10 The molar ratio of phosphorous acid to the conjugated compound is approximately
0.5:1 to 10:1, and the molar ratio of phosphonic acid to silylating agent is about 0.2:1 to 1:
10. The method according to item 9 above, used within the range of 10. 11 R of the phosphorous acid or its ester is lower alkyl, and Z in the conjugated compound is -
The method according to the above item 1, which is COOH or [Formula]. 12 The phosphonite is used in a molar ratio of about 0.5:1 to 10:1 with the conjugate compound, and the molar ratio of the phosphonite to the silylating agent is in the range of about 0.2:1 to 1:10. Said 11th used within the range
The method described in section. 13. The method according to item 1 above, wherein R in the phosphonic acid or its ester is H, and Z in the conjugated compound is -COOH or [Formula]. 14 The molar ratio of phosphorous acid to the conjugated compound is approximately
0.5:1 to 10:1, and the molar ratio of phosphorous acid to silylating agent is about 0.1:1 to 1:
15. The method according to item 13 above. 15. The method according to item 1 above, wherein the reaction of the phosphorous acid or its ester and the conjugated compound is carried out at a temperature within the range of 0 to 120°C. 16. The method according to item 1 above, wherein the phosphorous acid has the formula: the conjugated compound is H 2 C=CHCN, and the silylating agents are (CH 3 ) 3 SiCl and (C 2 H 5 ) 3 N.
JP59195642A 1983-09-19 1984-09-17 Manufacture of phosphinic acid intermediate Granted JPS6087293A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US53348683A 1983-09-19 1983-09-19
US533486 1983-09-19

Publications (2)

Publication Number Publication Date
JPS6087293A JPS6087293A (en) 1985-05-16
JPH0473437B2 true JPH0473437B2 (en) 1992-11-20

Family

ID=24126167

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Application Number Title Priority Date Filing Date
JP59195642A Granted JPS6087293A (en) 1983-09-19 1984-09-17 Manufacture of phosphinic acid intermediate

Country Status (6)

Country Link
JP (1) JPS6087293A (en)
CA (1) CA1258458A (en)
DE (1) DE3434124A1 (en)
FR (1) FR2552090B1 (en)
GB (1) GB2146644B (en)
IT (1) IT1176710B (en)

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DE102006010352A1 (en) * 2006-03-07 2007-09-13 Clariant International Limited Mixtures of mono-carboxyl-functionalized dialkylphosphinic salts and other components, a process for their preparation and use
CN102177164B (en) * 2008-11-05 2015-02-11 科莱恩金融(Bvi)有限公叞 Method for producing dialkylphosphinic acids and esters and salts thereof by means of allyl alcohols/acroleins and use thereof
DE102008055914A1 (en) * 2008-11-05 2010-05-06 Clariant International Limited A process for the preparation of mono-hydroxy-functionalized dialkylphosphinic acids, esters and salts by means of acroleins and their use
DE102008056341A1 (en) * 2008-11-07 2010-05-12 Clariant International Limited Process for the preparation of mono-amino-functionalized dialkylphosphinic acids, esters and salts by means of acrylonitriles and their use

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Publication number Priority date Publication date Assignee Title
US4168267A (en) * 1978-10-23 1979-09-18 E. R. Squibb & Sons, Inc. Phosphinylalkanoyl prolines

Also Published As

Publication number Publication date
FR2552090B1 (en) 1987-01-09
GB2146644A (en) 1985-04-24
GB2146644B (en) 1987-05-13
IT1176710B (en) 1987-08-18
CA1258458A (en) 1989-08-15
JPS6087293A (en) 1985-05-16
DE3434124A1 (en) 1985-04-04
IT8422707A0 (en) 1984-09-18
DE3434124C2 (en) 1993-07-01
FR2552090A1 (en) 1985-03-22
GB8423458D0 (en) 1984-10-24

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