JPH0524145B2 - - Google Patents
Info
- Publication number
- JPH0524145B2 JPH0524145B2 JP5528184A JP5528184A JPH0524145B2 JP H0524145 B2 JPH0524145 B2 JP H0524145B2 JP 5528184 A JP5528184 A JP 5528184A JP 5528184 A JP5528184 A JP 5528184A JP H0524145 B2 JPH0524145 B2 JP H0524145B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- compound represented
- general formula
- reaction
- addition salt
- 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
Links
- 239000002253 acid Substances 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- NSDYIDKTTPXCRH-UHFFFAOYSA-N 6-guanidinohexanoic acid Chemical compound NC(=N)NCCCCCC(O)=O NSDYIDKTTPXCRH-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- -1 p-hydroxybenzoic acid ester Chemical class 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- BVHDLCMLWONHHK-UHFFFAOYSA-N 6-(diaminomethylideneamino)hexanoic acid;hydrochloride Chemical compound Cl.NC(=N)NCCCCCC(O)=O BVHDLCMLWONHHK-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000000288 anti-kallikrein effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- DNTNDFLIKUKKOC-UHFFFAOYSA-N gabexate methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=C(OC(=O)CCCCCN=C(N)[NH3+])C=C1 DNTNDFLIKUKKOC-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は抗カリクレイン作用を有し、医薬とし
て有用な一般式〔〕
（式中、Ｒは低級アルキル基を表わす）
で示される化合物の酸付加塩の新規な製造方法に
関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention has an anti-kallikrein effect and is useful as a pharmaceutical. (In the formula, R represents a lower alkyl group.) The present invention relates to a novel method for producing an acid addition salt of a compound represented by the following formula.
従来この種の化合物の製法としては、例えば酸
ハロゲン化物とフエノール類の反応により酸クロ
ライド法（特公昭49−2107）、あるいはＮ，N′−
ジシクロヘキシルカルボジイミドの存在下、カル
ボン酸類とフエノール類との反応による縮合法
（特公昭57−34828）などが知られている。 Conventional methods for producing this type of compound include, for example, the acid chloride method (Japanese Patent Publication No. 49-2107), which involves the reaction of acid halides and phenols, or the N,N'-
A condensation method involving the reaction of carboxylic acids and phenols in the presence of dicyclohexylcarbodiimide (Japanese Patent Publication No. 57-34828) is known.
しかし、酸クロライド法は副反応の危険や悪臭
発生の難点がある。 However, the acid chloride method has drawbacks such as the risk of side reactions and the generation of bad odors.
また、前記縮合法は試薬のＮ，N′−ジシクロ
ヘキシルカルボジイミドが有毒かつ高価であり、
生成物に含有するジシクロヘキシルウレアを分離
しなければならないという欠点がある。そのため
に酸クロライド法あるいは縮合法は工業上必ずし
も満足しうるものではなかつた。 Furthermore, in the condensation method, the reagent N,N'-dicyclohexylcarbodiimide is toxic and expensive;
A disadvantage is that the dicyclohexylurea contained in the product must be separated. Therefore, the acid chloride method or the condensation method has not always been industrially satisfactory.
本発明者らはこれらの問題を解決するため種々
研究した結果、ε−グアニジノカプロン酸の酸付
加塩に一般式〔〕
（式中、Ｒは低級アルキル基を表わす）
で示される化合物を作用させることにより、一般
式〔〕
（式中、Ｒは前記と同じ意味を表わす）
で示される化合物の酸付加塩を有利に製造しうる
ことを見出した。 As a result of various studies to solve these problems, the present inventors found that the acid addition salt of ε-guanidinocaproic acid has the general formula [] (In the formula, R represents a lower alkyl group) By reacting with a compound represented by the general formula [] It has been found that an acid addition salt of a compound represented by the formula (wherein R has the same meaning as above) can be advantageously produced.
本発明方法によれば、簡単かつ経済的な手段で
一般式〔〕の酸付加塩が高収率及び良好な純度
で得られる。 According to the method of the present invention, acid addition salts of general formula [] can be obtained in high yield and good purity by simple and economical means.
反応は、ジメチルホルムアミド、ジメチルアセ
トアミド、ジメチルスルホキサイドなど反応に関
与しない溶媒中、0°〜60℃好ましくは15°〜30℃
で10〜30時間撹拌することにより容易に行われ
る。好ましくはピリジン、トリエチルアミンなど
の有機塩基の存在下行われる。 The reaction is carried out at 0° to 60°C, preferably at 15° to 30°C, in a solvent that does not participate in the reaction, such as dimethylformamide, dimethylacetamide, or dimethyl sulfoxide.
This is easily done by stirring for 10 to 30 hours. It is preferably carried out in the presence of an organic base such as pyridine or triethylamine.
ε−グアニジノカプロン酸と酸付加塩を形成す
る酸としては塩酸、臭化水素酸、硫酸、トルエン
スルホン酸、メタンスルホン酸などがあげられ
る。 Examples of acids that form acid addition salts with ε-guanidinocaproic acid include hydrochloric acid, hydrobromic acid, sulfuric acid, toluenesulfonic acid, and methanesulfonic acid.
本発明方法において用いられる一般式〔〕で
示される化合物は、ｐ−ヒドロキシ安息香酸エス
テルにハロゲン化チオニルを脱酸剤の存在下に反
応させることにより容易に得られる。 The compound represented by the general formula [] used in the method of the present invention can be easily obtained by reacting p-hydroxybenzoic acid ester with thionyl halide in the presence of a deoxidizing agent.
この反応において用いられる脱酸剤は、反応の
進行につれて副生するハロゲン化水素を捕捉、不
活性化するつもりであり、トリエチルアミン、ト
リブチルアミン、ジメチルアニリンなどの三級ア
ミン類が特に好ましい。反応はエーテル、ベンゼ
ン、トルエン、キシレンなどの溶媒中、０℃〜室
温で２〜10時間撹拌することにより容易に行われ
る。 The deoxidizing agent used in this reaction is intended to capture and inactivate hydrogen halide produced as a by-product as the reaction progresses, and tertiary amines such as triethylamine, tributylamine, and dimethylaniline are particularly preferred. The reaction is easily carried out in a solvent such as ether, benzene, toluene, xylene, etc. by stirring at 0° C. to room temperature for 2 to 10 hours.
本発明方法を工業的に実施する場合、ｐ−ヒド
ロキシ安息香酸から一般式〔〕で示される化合
物を製造し、これを単離することなくそのままε
−グアニジノカブロン酸の酸付加塩を反応させ
て、一般式〔〕で示される目的化合物を製造す
ることもできる。 When the method of the present invention is carried out industrially, the compound represented by the general formula [] is produced from p-hydroxybenzoic acid, and it is directly ε without being isolated.
- The target compound represented by the general formula [] can also be produced by reacting an acid addition salt of guanidinocabronic acid.
本発明の目的化合物〔〕は反応液中で酸付加
塩の形で生成する。この塩を収率よく単離、精製
するために重炭酸ナトリウム水溶液にて一度、炭
酸塩として取り出すことが望ましい。 The object compound of the present invention [ ] is produced in the form of an acid addition salt in the reaction solution. In order to isolate and purify this salt with good yield, it is desirable to take it out as a carbonate in an aqueous sodium bicarbonate solution.
一般式〔〕で示される化合物は必要により薬
理学的に許容され得る酸付加塩にたやすく変換す
ることができる。このような酸としては例えば塩
酸、臭化水素酸、メタンスルホン酸、トルエンス
ルホン酸、フマル酸、酒石酸などがあげられる。 The compound represented by the general formula [] can be easily converted into a pharmacologically acceptable acid addition salt if necessary. Examples of such acids include hydrochloric acid, hydrobromic acid, methanesulfonic acid, toluenesulfonic acid, fumaric acid, and tartaric acid.
次に実施例をあげて本発明を説明する。 Next, the present invention will be explained with reference to Examples.
実施例
ε−グアニジノカプロン酸ｐ−エトキシカルボ
ニルフエニルエステルメタンスルホン酸塩
ε−グアニジノカプロン酸塩酸塩1.05ｇ、ビス
（ｐ−エトキシカルボニルフエニル）スルフアイ
ト2.1ｇ、及び乾燥ジメチルホルムアミド３mlの
混合物を撹拌し、これに乾燥ピリジン1.5mlを加
え室温で20時間撹拌した。減圧下溶媒を留去し、
残留物にイソプロピルエーテル20mlを加え約５分
間撹拌した。イソプロピルエーテルをデカンテー
シヨンにより除去し、残渣にイソプロピルエーテ
ール20ml及び水10mlを加えて撹拌した。水層を分
取し、有機層を水３mlで抽出した。水層を合わ
せ、これに氷冷下飽和重曹水10mlを加え20分間撹
拌した。生成した沈澱物を取し、水、イソプロ
ピルエーテルの順に洗浄し、乾燥することにより
白色粉末1.8ｇを得た。Example ε-Guanidinocaproic acid p-ethoxycarbonylphenyl ester methanesulfonate A mixture of 1.05 g of ε-guanidinocaproic acid hydrochloride, 2.1 g of bis(p-ethoxycarbonylphenyl)sulfite, and 3 ml of dry dimethylformamide is stirred. Then, 1.5 ml of dry pyridine was added thereto, and the mixture was stirred at room temperature for 20 hours. The solvent was distilled off under reduced pressure,
20 ml of isopropyl ether was added to the residue and stirred for about 5 minutes. Isopropyl ether was removed by decantation, and 20 ml of isopropyl ether and 10 ml of water were added to the residue and stirred. The aqueous layer was separated, and the organic layer was extracted with 3 ml of water. The aqueous layers were combined, and 10 ml of saturated sodium bicarbonate solution was added to the mixture under ice cooling, and the mixture was stirred for 20 minutes. The resulting precipitate was collected, washed successively with water and isopropyl ether, and dried to obtain 1.8 g of white powder.
得られた粉末１ｇをとり、これをアセトン20ml
に懸濁させた。この懸濁液にメタンスルホン酸
0.25ｇを加え溶液とした。この溶液にエーテル40
mlを加え、生成した結晶を取し、エーテルで洗
浄した後乾燥させてmp91〜93℃の無色針状晶と
して目的化合物1.0ｇを得た（83％）。 Take 1g of the obtained powder and add it to 20ml of acetone.
suspended in. Add methanesulfonic acid to this suspension.
0.25g was added to form a solution. Ether 40 to this solution
ml was added, and the formed crystals were collected, washed with ether, and dried to obtain 1.0 g of the target compound (83%) as colorless needle crystals with a mp of 91 to 93°C.
IRνKBr naxcm-1：3500〜3200（NH）
1755、1710（Ｃ＝Ｏ）
1670、1630（グアニジウム塩）
1200、1050（SO2）
NMR（CD3OD）δ：1.36（3H、ｔ、Ｊ＝８Hz、−
ＣＨ 3）
1.30−2.00（6H、ｍ、−（ＣＨ 2）3−）
2.63（2H、ｔ、Ｊ＝７Hz、−ＣＨ 2COO）
2.78（3H、ｓ、ＣＨ 3SO3H）
3.00−3.30（2H、ｍ、−ＣＨ 2NH−）
4.32（2H、ｑ、Ｊ＝８Hz、−ＣＨ 2CH3）
7.04〜8.08（4H、ｍ、芳香族水素）
参考例
ビス（ｐ−エトキシカルボニルフエニル）スル
フアイト
ｐ−ハイドロキシ安息香酸エチル16.6ｇ及び乾
燥エーテル100mlを氷冷しながら撹拌した。これ
にチオニルクロライド６ｇを加えた。この混合物
にトリエチルアミン10.1ｇを含有する乾燥エーテ
ル溶液20mlを15分を要して滴下した。反応混合物
を室温にて一夜放置した後不溶物を去し、エー
テルで洗浄した。液と洗液を合わせた後溶媒を
留去することにより淡かつ色油状物としてビス
（ｐ−エトキシカルボニルフエニル）スルフアイ
ト19ｇを得た。IRν KBr nax cm -1 : 3500-3200 (NH) 1755, 1710 (C=O) 1670, 1630 (guanidium salt) 1200, 1050 (SO 2 ) NMR (CD 3 OD) δ: 1.36 (3H, t, J =8Hz, -
C H 3 ) 1.30−2.00 (6H, m, −(C H 2 ) 3 −) 2.63 (2H, t, J=7Hz, −C H 2 COO) 2.78 (3H, s, C H 3 SO 3 H) 3.00-3.30 (2H, m, -CH 2 NH-) 4.32 (2H, q, J=8Hz, -CH 2 CH 3 ) 7.04-8.08 (4H, m, aromatic hydrogen) Reference example bis (p- Ethoxycarbonylphenyl) sulfite 16.6 g of ethyl p-hydroxybenzoate and 100 ml of dry ether were stirred while cooling with ice. To this was added 6 g of thionyl chloride. 20 ml of a dry ether solution containing 10.1 g of triethylamine was added dropwise to this mixture over a period of 15 minutes. After the reaction mixture was left at room temperature overnight, insoluble materials were removed and washed with ether. After combining the liquid and the washing liquid, the solvent was distilled off to obtain 19 g of bis(p-ethoxycarbonylphenyl)sulfite as a pale and colored oil.
IRνNaCl naxcm-1：1715（Ｃ＝Ｏ）
1270（Ｓ＝Ｏ）
NMR（CDCl3）δ：1.80（3H、ｔ、Ｊ＝８Hz、−
ＣＨ 3CH2）
4.80（2H、ｑ、Ｊ＝８Hz、CH3CＨ 2−
7.10〜8.20（4H、ｍ、芳香族水素）IRν NaCl nax cm -1 : 1715 (C=O) 1270 (S=O) NMR (CDCl 3 ) δ: 1.80 (3H, t, J=8Hz, -
C H 3 CH 2 ) 4.80 (2H, q, J=8Hz, CH 3 C H 2 − 7.10 to 8.20 (4H, m, aromatic hydrogen)
Claims (1)
式 （式中、Ｒは低級アルキル基を表わす） で示される化合物を作用させることを特徴とする
一般式 （式中、Ｒは前記と同じ意味を表わす） で示される化合物の酸付加塩の製造方法。[Claims] 1 The acid addition salt of ε-guanidinocaproic acid has the general formula (In the formula, R represents a lower alkyl group) A general formula characterized by acting on a compound represented by (In the formula, R represents the same meaning as above.) A method for producing an acid addition salt of a compound represented by the following.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5528184A JPS60199869A (en) | 1984-03-24 | 1984-03-24 | Esterification |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5528184A JPS60199869A (en) | 1984-03-24 | 1984-03-24 | Esterification |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60199869A JPS60199869A (en) | 1985-10-09 |
| JPH0524145B2 true JPH0524145B2 (en) | 1993-04-06 |
Family
ID=12994202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5528184A Granted JPS60199869A (en) | 1984-03-24 | 1984-03-24 | Esterification |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60199869A (en) |
-
1984
- 1984-03-24 JP JP5528184A patent/JPS60199869A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60199869A (en) | 1985-10-09 |
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