JPH02184692A - Preparation of amonophosphinylbutyric acid hydrochloric acid salt - Google Patents
Preparation of amonophosphinylbutyric acid hydrochloric acid saltInfo
- Publication number
- JPH02184692A JPH02184692A JP398589A JP398589A JPH02184692A JP H02184692 A JPH02184692 A JP H02184692A JP 398589 A JP398589 A JP 398589A JP 398589 A JP398589 A JP 398589A JP H02184692 A JPH02184692 A JP H02184692A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- lower alkyl
- hydrochloric acid
- substituted
- phenyl
- 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.)
- Pending
Links
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 239000002253 acid Substances 0.000 title claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- -1 (substituted) phenyl Chemical group 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 8
- 150000002148 esters Chemical class 0.000 claims abstract description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 4
- 150000002576 ketones Chemical class 0.000 claims abstract description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 6
- 238000006297 dehydration reaction Methods 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- 150000003839 salts Chemical class 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- YQXUEAFBCGTZHL-UHFFFAOYSA-N NP(=O)C(C(=O)O)CC Chemical compound NP(=O)C(C(=O)O)CC YQXUEAFBCGTZHL-UHFFFAOYSA-N 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- UPHFOMRDMBRJBA-UHFFFAOYSA-N NP(Cl)=O Chemical compound NP(Cl)=O UPHFOMRDMBRJBA-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- PIJXRNNCIJAUOX-UHFFFAOYSA-N butanoic acid;hydrochloride Chemical compound Cl.CCCC(O)=O PIJXRNNCIJAUOX-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 1
- IDBRULKICVRMNG-UHFFFAOYSA-N 2-amino-4-hydroxyphosphonoylbutanoic acid Chemical compound OC(=O)C(N)CCP(O)=O IDBRULKICVRMNG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- BGFHICLSSBIRCW-UHFFFAOYSA-N C(C)OP(=O)CC=C Chemical compound C(C)OP(=O)CC=C BGFHICLSSBIRCW-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical group ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XKVAYWWAUYBUSM-UHFFFAOYSA-N Cl.OC(=O)C(N)CCP(=O)CO Chemical compound Cl.OC(=O)C(N)CCP(=O)CO XKVAYWWAUYBUSM-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FNJQGUKETYGBGL-UHFFFAOYSA-N OC(=O)C(N)CCP(=O)CO Chemical class OC(=O)C(N)CCP(=O)CO FNJQGUKETYGBGL-UHFFFAOYSA-N 0.000 description 1
- DYEQYKMIWLHCOI-UHFFFAOYSA-N OCP(=O)C(C(=O)O)CC Chemical compound OCP(=O)C(C(=O)O)CC DYEQYKMIWLHCOI-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical class 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000007033 dehydrochlorination reaction Methods 0.000 description 1
- MQIKJSYMMJWAMP-UHFFFAOYSA-N dicobalt octacarbonyl Chemical group [Co+2].[Co+2].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] MQIKJSYMMJWAMP-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001624 naphthyl group Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004076 pyridyl group Chemical class 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（イ）産業上の利用分野
本発明は、除草剤の有効成分化合物として有用なアミノ
ホスフィニル酪酸の塩酸塩の製造法に関するものである
。DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application The present invention relates to a method for producing aminophosphinylbutyric acid hydrochloride, which is useful as an active ingredient compound of herbicides.
（ロ）従来の技術
従来、アミノホスフィニル酪酸の製造法としては特願昭
６３−５９８７２号等が挙げられる。(B) Prior art Conventional methods for producing aminophosphinylbutyric acid include Japanese Patent Application No. 1983-59872.
この方法は、ビニルホスフィン酸アルキルエステルをコ
バルト触媒存在下、アミドカルボニル化反応を行いＮ−
アシルアミノホスフィニル酪酸誘導体を製造後、塩酸水
溶液により加水分解してアミノホスフィニル酪酸塩酸塩
とし、更にアルカリによる中和、溶媒による再結晶を行
うことによりアミノホスフィニル酪酸を得ている。In this method, vinylphosphinate alkyl ester is subjected to an amide carbonylation reaction in the presence of a cobalt catalyst.
After producing an acylaminophosphinylbutyric acid derivative, it is hydrolyzed with an aqueous hydrochloric acid solution to produce aminophosphinylbutyric acid hydrochloride, and then neutralized with an alkali and recrystallized with a solvent to obtain aminophosphinylbutyric acid. .
しかし、この方法はアミノホスフィニル酪酸の水溶性が
高いため、再結晶法によりアミノホスフィニル酪酸を収
率よく得ることは困難である。However, in this method, it is difficult to obtain aminophosphinylbutyric acid in good yield by recrystallization because aminophosphinylbutyric acid has high water solubility.
又、アミノホスフィニル酪酸塩酸塩の水溶性は更に高い
ため、再結晶法によりアミノホスフィニル酪酸塩酸塩を
収率よく得ることは殊更困難である。Furthermore, since the water solubility of aminophosphinyl butyrate hydrochloride is even higher, it is particularly difficult to obtain aminophosphinyl butyrate hydrochloride in good yield by a recrystallization method.
（ハ）問題点を解決するための手段
本発明者らは、除草剤の有効成分化合物として有用なア
ミノホスフィニル酪酸の塩酸塩の製造法について種々検
討した結果、Ｎ−アシルアミノホスフィニル酪酸を塩酸
存在下加水分解後、生成した粗アミノホスフィニル酪酸
塩酸塩を再結晶することなく、又は粗アミノホスフィニ
ル酪酸塩酸塩とプロピレンオキサイド等との反応を行い
アミノホスフィニル酪酸とすることなく、溶媒による粗
アミノホスフィニル酪酸塩酸塩の洗浄のみで容易に高純
度のアミノホスフィニル酪酸塩酸塩が得られることを見
出し本発明を完成するに至った。(c) Means for solving the problem As a result of various studies on the production method of aminophosphinylbutyric acid hydrochloride, which is useful as an active ingredient compound of herbicides, the present inventors found that N-acylaminophosphinylbutyric acid After hydrolyzing butyric acid in the presence of hydrochloric acid, the resulting crude aminophosphinylbutyric acid hydrochloride can be converted into aminophosphinylbutyric acid without recrystallizing it, or by reacting the crude aminophosphinylbutyric acid hydrochloride with propylene oxide, etc. The present inventors have discovered that highly pure aminophosphinyl butyrate hydrochloride can be easily obtained simply by washing the crude aminophosphinyl butyrate hydrochloride with a solvent, and have completed the present invention.
即ち、本発明は一般式（ＩＩ）
（式中、Ｒ１は低級アルキル基、Ｒ２は水素、低級アル
キル基、ハロ低級アルキル基又は置換されていてもよい
フェニル基、Ｒ３はアルキル基又は置換されていてもよ
いフェニル基を示す。）で表されるＮ−アシルアミノホ
スフィニル酪酸を塩酸存在下加水分解し、生成した粗ア
ミノホスフィニル酪酸塩酸塩を乾燥後、アルコール類、
水溶性エーテル類、ケトン類、エステル類から選ばれる
１種以上の溶媒で洗浄することを特徴とする一般式〔■
〕
で表されるアミノホスフィニル酪酸塩酸塩の製造法に関
するものである。That is, the present invention relates to the general formula (II) (wherein R1 is a lower alkyl group, R2 is hydrogen, a lower alkyl group, a halo-lower alkyl group, or an optionally substituted phenyl group, and R3 is an alkyl group or a substituted phenyl group). N-acylaminophosphinylbutyric acid represented by (representing a phenyl group that may be used) is hydrolyzed in the presence of hydrochloric acid, and the resulting crude aminophosphinylbutyric acid hydrochloride is dried, and then alcohols,
A general formula characterized by washing with one or more solvents selected from water-soluble ethers, ketones, and esters [■
] This relates to a method for producing aminophosphinyl butyrate hydrochloride represented by:
本発明において、置換基のＲ’ としては、例えばメチ
ル、エチル、ノルマルプロピル、イソプロピル、ノルマ
ルブチル、イソブチル、ターシャリブチル基等の低級ア
ルキル基が挙げられるが、これらの中でメチル基が好ま
しいものである。In the present invention, examples of the substituent R' include lower alkyl groups such as methyl, ethyl, normal propyl, isopropyl, normal butyl, isobutyl, and tert-butyl groups, and among these, methyl group is preferred. It is.
置換基Ｒ２としては、例えば水素、メチル、エチル、ノ
ルマルプロピル、イソプロピル、ノルマルブチル、イソ
ブチル、ターシャリブチル等の低級アルキル基、ハロゲ
ノメチル、ハロゲノエチル、ハロゲノプロピル、ハロゲ
ノブチル等のハロ低級アルキル基、フェニル及びベンジ
ル等の置換されていてもよいフェニル基が挙げられる。Examples of the substituent R2 include hydrogen, lower alkyl groups such as methyl, ethyl, normal propyl, isopropyl, normal butyl, isobutyl, and tertiary butyl; halo lower alkyl groups such as halogenomethyl, halogenoethyl, halogenopropyl, and halogenobutyl; Examples include optionally substituted phenyl groups such as phenyl and benzyl.
ハロ低級アルキル基のハロゲンとしては、塩素、弗素、
沃素、臭素が挙げられる。Examples of the halogen in the halo-lower alkyl group include chlorine, fluorine,
Examples include iodine and bromine.
置換されていてもよいフェニル基の置換基は特に限定さ
れるものではなく、例えば低級アルキル基、ハロゲン等
が挙げられる。The substituents of the phenyl group which may be substituted are not particularly limited, and examples thereof include lower alkyl groups and halogens.
ハロゲンとしては、塩素、弗素、沃素、臭素が挙げられ
る。Examples of halogen include chlorine, fluorine, iodine, and bromine.
上記置換基Ｒ２の中で、メチル、１−クロルエチル、２
−クロルエチル基等が好ましいものである。Among the above substituents R2, methyl, 1-chloroethyl, 2
-Chlorethyl group and the like are preferred.
置換基Ｒ３としては、例えば水素、メチル、エチル、ノ
ルマルプロピル、イソプロピル、ノルマルブチル、イソ
ブチル、ターシャリブチル、ドデシル等のアルキル基、
フェニル、メチル置換フェニル、トリメチル置換フェニ
ル、ブチル置換フェニル、メトキシ置換フェニル、シア
ノ置換フェニル、弗素置換フェニル、２弗素置換フエニ
ル、弗素及び塩素で置換されたフェニル、塩素置換フェ
ニル、２塩素置換フエニル、メチル及び塩素で置換され
たフェニル、臭素置換フェニル、ベンゾイル置換フェニ
ル、メチル置換フェニルブチル、ナフチル及びベンジル
等の置換されていてもよいフェニル基、ピリジニル基及
びアミノ基等が挙げられるが、メチル基、フェニル基が
好ましい。Examples of the substituent R3 include hydrogen, alkyl groups such as methyl, ethyl, normal propyl, isopropyl, normal butyl, isobutyl, tert-butyl, and dodecyl;
Phenyl, methyl substituted phenyl, trimethyl substituted phenyl, butyl substituted phenyl, methoxy substituted phenyl, cyano substituted phenyl, fluorine substituted phenyl, difluorine substituted phenyl, phenyl substituted with fluorine and chlorine, chlorine substituted phenyl, dichlorine substituted phenyl, methyl and optionally substituted phenyl groups such as chlorine-substituted phenyl, bromine-substituted phenyl, benzoyl-substituted phenyl, methyl-substituted phenylbutyl, naphthyl, and benzyl, pyridinyl groups, and amino groups. Groups are preferred.
一般式（ＩＩ）のＮ−アシルアミノホスフィニル酪酸の
加水分解に使用される塩酸としては、通常１〜２８重量
％の水溶液が採用され、好ましくは１０〜２０重量％の
水溶液がよい。The hydrochloric acid used in the hydrolysis of N-acylaminophosphinylbutyric acid of general formula (II) is usually a 1-28% by weight aqueous solution, preferably a 10-20% by weight aqueous solution.
塩酸の量は特に規定されないが、一般式（ＩＩ）のＮ−
アシルホスフィニルアミノ酪酸１当量に対して通常等量
以上の塩酸が使用され、好ましくは５〜１０当量がよい
。Although the amount of hydrochloric acid is not particularly limited, N-
An equivalent or more amount of hydrochloric acid is usually used per equivalent of acylphosphinyl aminobutyric acid, preferably 5 to 10 equivalents.
加水分解の温度としては、通常５０〜１００°Ｃが採用
され、好ましくは８０〜１００°Ｃがよい。The hydrolysis temperature is usually 50 to 100°C, preferably 80 to 100°C.
加水分解の時間としては、通常１〜５時間が採用され、
好ましくは１〜３時間がよい。The hydrolysis time is usually 1 to 5 hours,
Preferably, the time is 1 to 3 hours.
粗アミノホスフィニル酪酸塩酸塩の脱水温度としては、
通常５０〜１００℃が採用され、好ましくは７０〜８０
°Ｃがよい。The dehydration temperature of crude aminophosphinyl butyric acid hydrochloride is:
Usually 50 to 100°C, preferably 70 to 80°C.
°C is good.
脱水時間としては、通常１〜５時間が採用され、好まし
くは１〜３時間がよい。The dehydration time is usually 1 to 5 hours, preferably 1 to 3 hours.
脱水方法としては、通常の常圧下及び減圧下の脱水方法
の他、例えばベンゼン、トルエン等による共沸脱水法等
も採用することができる。As the dehydration method, in addition to the usual dehydration methods under normal pressure and reduced pressure, for example, azeotropic dehydration using benzene, toluene, etc. can be employed.
粗アミノホスフィニル酪酸塩酸塩の洗浄に使用される溶
媒としては、メタノール、エタノール、プロパツール等
の炭素数１〜５のアルコール類、ジオキサン、テトラハ
イドロフラン等の水溶性エーテル類、アセトン、メチル
エチルケトン、アセトフェノン等のケトン類、酢酸メチ
ル、酢酸エチル等のエステル類が挙げられる。Solvents used for washing crude aminophosphinyl butyric acid hydrochloride include alcohols having 1 to 5 carbon atoms such as methanol, ethanol, and propatool, water-soluble ethers such as dioxane and tetrahydrofuran, acetone, and methyl ethyl ketone. , ketones such as acetophenone, and esters such as methyl acetate and ethyl acetate.
洗浄に使用される溶媒の量は特に限定されないが、粗ア
ミノホスフィニル酪酸塩酸塩１重量部に対して通常０．
５〜５０重量部が使用され、好ましくは２〜２０重量部
が使用される。The amount of solvent used for washing is not particularly limited, but is usually 0.
5 to 50 parts by weight are used, preferably 2 to 20 parts by weight.
洗浄温度は特に限定されないが、通常３０〜５０°Ｃが
採用され、好ましくは３０〜４０°Ｃがよい。Although the washing temperature is not particularly limited, it is usually 30 to 50°C, preferably 30 to 40°C.
（ニ）発明の効果
本発明の製造法により、Ｎ−アシルアミノホスフィニル
酪酸を塩酸存在下加水分解後、生成した粗アミノホスフ
ィニル酪酸塩酸塩を再結晶することなく、溶媒による洗
浄のみで容易に高純度の一般式（１）のアミノホスフィ
ニル酸塩酸塩を高収率で得ることができる。(d) Effects of the invention By the production method of the present invention, after hydrolyzing N-acylaminophosphinylbutyric acid in the presence of hydrochloric acid, the resulting crude aminophosphinylbutyric acid hydrochloride is not recrystallized, but only washed with a solvent. A highly purified aminophosphinyl hydrochloride of general formula (1) can be easily obtained in high yield.
又、生成した一般式（１）のアミノホスフィニル酸塩酸
塩を通常の脱塩酸方法、例えばエチレンオキサイド、プ
ロピレンオキサイド等と反応させることにより、高純度
のアミノホスフィニル酪酸を高収率で得ることができる
。In addition, by reacting the produced aminophosphinyl hydrochloride of general formula (1) with a conventional dehydrochlorination method, for example, with ethylene oxide, propylene oxide, etc., high purity aminophosphinyl butyric acid can be produced in high yield. Obtainable.
（ホ）実施例
以下、本発明について実施例を挙げて説明するが本発明
はこれらに限定されるものではない。(e) Examples The present invention will be described below with reference to Examples, but the present invention is not limited to these.
実施例１
Ｈ
１００ｍｆのステンレス製オートクレーブにジオキサン
５０ｇ１ビニルメチルホスフイン酸エチル３．８５ｇ、
アセトアミド１．７７ｇ及びジコバルトオクタカルボニ
ル１０３ｍｇを仕込んだ。Example 1 H In a 100 mf stainless steel autoclave, 50 g of dioxane 1 3.85 g of ethyl vinylmethylphosphinate;
1.77 g of acetamide and 103 mg of dicobalt octacarbonyl were charged.
オートクレーブを一酸化炭素と水素との混合ガス（１：
１モル比）で置換して１００°０１１２０ｋｇ／ｃｍ”
Ｇで４時間反応させた。The autoclave was heated with a mixed gas of carbon monoxide and hydrogen (1:
1 molar ratio) to 100°01120kg/cm”
G for 4 hours.
オートクレーブを冷却後、反応生成物を取り出し溶媒を
除去後、生成物を１５重量％塩酸水溶液７５ｇを使用し
て、１００°Ｃで３時間加水分解して２−アミノ−４−
ヒドロキシメチルホスフィニル酪酸の塩酸塩水溶液を得
た。この水溶液を乾固して粗２−アミノー４−ヒドロキ
シメチルホスフィニル酪酸塩酸塩６．２ｇを得た。After cooling the autoclave, the reaction product was taken out, the solvent was removed, and the product was hydrolyzed using 75 g of a 15% by weight aqueous hydrochloric acid solution at 100°C for 3 hours to obtain 2-amino-4-
An aqueous hydrochloride solution of hydroxymethylphosphinylbutyric acid was obtained. This aqueous solution was dried to obtain 6.2 g of crude 2-amino-4-hydroxymethylphosphinyl butyric acid hydrochloride.
この粗塩酸塩固体に乾燥エタノール２０ｍ１を加えて２
０分撹拌し濾過後、エタノールを除去して、２−アミノ
−４−ヒドロキシルメチルホスフィニル酪酸塩酸塩６．
１ｇを得た。収率は９８％であり、純度は９９．９％で
あった。Add 20ml of dry ethanol to this crude hydrochloride solid and
After stirring for 0 minutes and filtration, ethanol was removed and 2-amino-4-hydroxylmethylphosphinylbutyric acid salt 6.
1g was obtained. The yield was 98% and the purity was 99.9%.
実施例２
実施例１と同様にして得た粗２−アミノー４−ヒドロキ
シメチルホスフィニル酪酸塩酸塩固体５゜０ｇをプロピ
レンオキサイド５０ｇと反応させた後、アセトン−水溶
媒（２：１体積比）１００ｍ！を使用して再結晶を行い
、２−アミノ−４−ヒドロキシホスフィニル酪酸２．１
ｇを得た。収率は５０％であり、純度は９７．８％であ
った。Example 2 5.0 g of crude 2-amino-4-hydroxymethylphosphinyl butyrate hydrochloride solid obtained in the same manner as in Example 1 was reacted with 50 g of propylene oxide, and then an acetone-water solvent (2:1 volume ratio) was reacted with 50 g of propylene oxide. )100m! Recrystallization was performed using 2-amino-4-hydroxyphosphinylbutyric acid 2.1
I got g. The yield was 50% and the purity was 97.8%.
実施例３
実施例１と同様にして得た粗２−アミノー４−ヒドロキ
シメチルホスフィニル酪酸塩酸塩固体５゜０ｇをエタノ
ール洗浄せずにアセトン−水溶媒（２：１体積比）１０
０ｍｆ！、を使用して再結晶を行ったが、塩酸塩の水溶
性が高いため結晶は析出しなかった。Example 3 5.0 g of crude 2-amino-4-hydroxymethylphosphinyl butyrate hydrochloride solid obtained in the same manner as in Example 1 was dissolved in an acetone-water solvent (2:1 volume ratio) 10 without washing with ethanol.
0mf! Recrystallization was performed using , but no crystals were precipitated because the hydrochloride is highly water-soluble.
Claims (2)
アルキル基、ハロ低級アルキル基又は置換されていても
よいフェニル基、Ｒ＾３はアルキル基又は置換されてい
てもよいフェニル基を示す。） で表されるＮ−アシルアミノホスフィニル酪酸を塩酸存
在下加水分解後、生成した粗ホスフィニルアミノ酪酸塩
酸塩を、アルコール類、水溶性エーテル類、ケトン類、
エステル類から選ばれる１種以上の溶媒で洗浄すること
を特徴とする 一般式〔 I 〕 ▲数式、化学式、表等があります▼〔 I 〕 で表されるアミノホスフィニル酪酸塩酸塩の製造法。(1) General formula [II] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [II] (In the formula, R^1 is a lower alkyl group, R^2 is hydrogen, a lower alkyl group, a halo-lower alkyl group, or a substituted R^3 represents an alkyl group or a phenyl group which may be substituted.) After hydrolyzing N-acylaminophosphinylbutyric acid in the presence of hydrochloric acid, Finylaminobutyric acid hydrochloride, alcohols, water-soluble ethers, ketones,
A method for producing aminophosphinyl butyric acid hydrochloride represented by the general formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼[I] characterized by washing with one or more solvents selected from esters .
ハロゲノエチル基、Ｒ＾３が低級アルキル基又はフェニ
ル基である請求項１記載の製造法。(2) The method according to claim 1, wherein R^1 is a methyl group, R^2 is hydrogen, a methyl group, or a halogenoethyl group, and R^3 is a lower alkyl group or a phenyl group.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP398589A JPH02184692A (en) | 1989-01-11 | 1989-01-11 | Preparation of amonophosphinylbutyric acid hydrochloric acid salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP398589A JPH02184692A (en) | 1989-01-11 | 1989-01-11 | Preparation of amonophosphinylbutyric acid hydrochloric acid salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02184692A true JPH02184692A (en) | 1990-07-19 |
Family
ID=11572322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP398589A Pending JPH02184692A (en) | 1989-01-11 | 1989-01-11 | Preparation of amonophosphinylbutyric acid hydrochloric acid salt |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02184692A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009511624A (en) * | 2005-10-18 | 2009-03-19 | サーントゥル ナシオナル ドゥ ラ ルシェルシュ シャーンティフィク （セ エン エール エス） | Hypophosphorous acid derivatives and therapeutic uses thereof |
| WO2011158813A1 (en) * | 2010-06-15 | 2011-12-22 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | Method for producing n-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid |
-
1989
- 1989-01-11 JP JP398589A patent/JPH02184692A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009511624A (en) * | 2005-10-18 | 2009-03-19 | サーントゥル ナシオナル ドゥ ラ ルシェルシュ シャーンティフィク （セ エン エール エス） | Hypophosphorous acid derivatives and therapeutic uses thereof |
| WO2011158813A1 (en) * | 2010-06-15 | 2011-12-22 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | Method for producing n-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid |
| JP5033933B2 (en) * | 2010-06-15 | 2012-09-26 | Ｍｅｉｊｉ Ｓｅｉｋａファルマ株式会社 | Process for producing N-substituted-2-amino-4- (hydroxymethylphosphinyl) -2-butenoic acid |
| US8481779B2 (en) | 2010-06-15 | 2013-07-09 | Meiji Seika Pharma Co., Ltd. | Method for producing N-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid |
| AU2011266126B2 (en) * | 2010-06-15 | 2014-12-11 | Meiji Seika Pharma Co., Ltd. | Method for producing N-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid |
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