JPH041736B2 - - Google Patents
Info
- Publication number
- JPH041736B2 JPH041736B2 JP21477883A JP21477883A JPH041736B2 JP H041736 B2 JPH041736 B2 JP H041736B2 JP 21477883 A JP21477883 A JP 21477883A JP 21477883 A JP21477883 A JP 21477883A JP H041736 B2 JPH041736 B2 JP H041736B2
- Authority
- JP
- Japan
- Prior art keywords
- methoxyphenyl
- formula
- chloro
- acetoxy
- reaction
- 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
Links
- -1 2-acetoxy-3-chloro-3- (4-methoxyphenyl)propionic acid alkyl ester compound Chemical class 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- AHXGRMIPHCAXFP-UHFFFAOYSA-L chromyl dichloride Chemical compound Cl[Cr](Cl)(=O)=O AHXGRMIPHCAXFP-UHFFFAOYSA-L 0.000 claims description 4
- 230000021736 acetylation Effects 0.000 claims 1
- 238000006640 acetylation reaction Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 9
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000000862 absorption spectrum Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011345 viscous material Substances 0.000 description 3
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000012345 acetylating agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- AZBWJFYDVNOHGD-UHFFFAOYSA-N methyl 3-chloro-2-hydroxy-3-(4-methoxyphenyl)propanoate Chemical compound COC(=O)C(O)C(Cl)C1=CC=C(OC)C=C1 AZBWJFYDVNOHGD-UHFFFAOYSA-N 0.000 description 2
- VEZIKIAGFYZTCI-UHFFFAOYSA-N methyl ester of p-methoxycinnamic acid Natural products COC(=O)C=CC1=CC=C(OC)C=C1 VEZIKIAGFYZTCI-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QZNNLFPIPTYBRV-UHFFFAOYSA-N 2-ethyl-2-(4-methoxyphenyl)butanoic acid Chemical compound CCC(CC)(C(O)=O)C1=CC=C(OC)C=C1 QZNNLFPIPTYBRV-UHFFFAOYSA-N 0.000 description 1
- LUJSTQMYFGYNDI-UHFFFAOYSA-N 5-[2-(dimethylamino)ethyl]-2,3-dihydro-1,5-benzothiazepin-4-one Chemical compound S1CCC(=O)N(CCN(C)C)C2=CC=CC=C21 LUJSTQMYFGYNDI-UHFFFAOYSA-N 0.000 description 1
- 241000234282 Allium Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- DALDUXIBIKGWTK-UHFFFAOYSA-N benzene;toluene Chemical compound C1=CC=CC=C1.CC1=CC=CC=C1 DALDUXIBIKGWTK-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- AFDXODALSZRGIH-UHFFFAOYSA-N p-coumaric acid methyl ether Natural products COC1=CC=C(C=CC(O)=O)C=C1 AFDXODALSZRGIH-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Description
【発明の詳細な説明】
本発明は、置換ｐ−メトキシフエニル化合物及
びその製造方法に関し、更に詳細には、式（）
（式中、Ｒは低級アルキル基を表わす）
で表わされる２−アセトキシ−３−クロロ−３−
（４−メトキシフエニル）プロピオン酸アルキル
エステル及びその製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a substituted p-methoxyphenyl compound and a method for producing the same, and more particularly, the present invention relates to a substituted p-methoxyphenyl compound and a method for producing the same, and more particularly, the present invention relates to a substituted p-methoxyphenyl compound and a method for producing the same. (In the formula, R represents a lower alkyl group) 2-acetoxy-3-chloro-3-
The present invention relates to a (4-methoxyphenyl)propionic acid alkyl ester and a method for producing the same.
本発明の目的化合物である式（）で表わされ
る２−アセトキシ−３−クロロ−３−（４−メト
キシフエニル）プロピオン酸アルキルエステルは
新規な化合物であり、医薬品の合成用中間体とし
て、就中、冠血管拡張作用を有する２−（４−メ
トキシフエニル）−３−アセトキシ−５−（２−ジ
メチルアミノエチル）−２，３−ジヒドロ−１，
５−ベンゾチアゼピン−４（5H）−オンの合成用
中間体として有用な化合物である。 The object compound of the present invention, 2-acetoxy-3-chloro-3-(4-methoxyphenyl)propionic acid alkyl ester represented by the formula (), is a new compound and is useful as an intermediate for the synthesis of pharmaceuticals. Among them, 2-(4-methoxyphenyl)-3-acetoxy-5-(2-dimethylaminoethyl)-2,3-dihydro-1, which has a coronary vasodilator effect.
It is a compound useful as an intermediate for the synthesis of 5-benzothiazepin-4(5H)-one.
上記式（）で表わされる化合物は、例えば次
の如き方法によつて製造される。 The compound represented by the above formula () can be produced, for example, by the following method.
（式中、Ｒは低級アルキル基を表わす）
反応工程図
即ち、式（）で表わされるｐ−メトキシケイ
皮酸アルキルエステルを有機溶媒中、塩化クロミ
ルと反応させ、式（）で表わされる２−ヒドロ
キシ−３−クロロ−３−（４−メトキシフエニル）
プロピオン酸アルキルエステルを生成し、次いで
この化合物をアセチル化することにより、式
（）で表わされる２−アセトキシ−３−クロロ
−３−（４−メトキシフエニル）プロピオン酸ア
ルキルエステルを製造することが出来る。 (In the formula, R represents a lower alkyl group) Reaction process diagram That is, a p-methoxycinnamic acid alkyl ester represented by the formula () is reacted with chromyl chloride in an organic solvent to form a 2- Hydroxy-3-chloro-3-(4-methoxyphenyl)
2-acetoxy-3-chloro-3-(4-methoxyphenyl)propionate alkyl ester represented by the formula () can be produced by producing a propionate alkyl ester and then acetylating this compound. I can do it.
本反応に於て使用される有機溶媒としては、ベ
ンゼントルエン、キシレン、アセトン、メタノー
ル、エタノール、クロロホルム、テトラヒドロフ
ラン、アセトニトリル、ジオキサン、四塩化炭
素、塩化メチレン、Ｎ，Ｎ−ジメチルスルホキシ
ド、Ｎ，Ｎ−ジメチルホルムアミド、ジエチルエ
ーテル、ジメチルエーテル、メチルエチルエーテ
ルなどが挙げられる。また、アセチル化剤として
は、ハロゲン化アセチル、酢酸、無水酢酸などが
挙げられる。 Organic solvents used in this reaction include benzene toluene, xylene, acetone, methanol, ethanol, chloroform, tetrahydrofuran, acetonitrile, dioxane, carbon tetrachloride, methylene chloride, N,N-dimethylsulfoxide, N,N- Examples include dimethylformamide, diethyl ether, dimethyl ether, methyl ethyl ether, and the like. Further, examples of the acetylating agent include halogenated acetyl, acetic acid, and acetic anhydride.
本反応は２段階で進行するが、中間生成物とし
ての式（）で表わされる化合物は、必要に応じ
て単離することが出来るが、単離することなくそ
のまま、次の反応へ利用することも出来る。 This reaction proceeds in two steps, and the compound represented by formula () as an intermediate product can be isolated if necessary, but it cannot be used as is for the next reaction without isolation. You can also do it.
本反応に於ては、反応化合物１モルに対して塩
化クロミル並びにアセチル化剤を等モル乃至やや
過剰モル量使用して、通常、冷却下乃至加熱環流
下の比較的緩和な反応条件下で行なわれ、反応時
間は使用する溶媒などにより多少異なるが、、約
30分乃至24時間である。 In this reaction, chromyl chloride and the acetylating agent are used in equimolar to slightly excess molar amounts per mole of the reaction compound, and the reaction is usually carried out under relatively mild reaction conditions, such as cooling or heating under reflux. The reaction time varies depending on the solvent used, but it is approximately
The duration ranges from 30 minutes to 24 hours.
反応終了後、生成した式（）で表わされる２
−アセトキシ−３−クロロ−３−（４−メトキシ
フエニル）プロピオン酸アルキルエステルを反応
混合物中から分離・精製するには、例えば溶媒抽
出、溶媒留去、カラムクロマトグラフイーなどの
公知の方法を適宜選択、組合せて用いることによ
り容易に実施することが出来る。 After the reaction is complete, the generated formula () is 2
-Acetoxy-3-chloro-3-(4-methoxyphenyl)propionic acid alkyl ester can be separated and purified from the reaction mixture using known methods such as solvent extraction, solvent distillation, and column chromatography. It can be easily implemented by appropriately selecting and using combinations.
次に、本発明に係る式（）で表わされる２−
アセトキシ−３−クロロ−３−（４−メトキシフ
エニル）プロピオン酸アルキルエステルを用いて
２−（４−メトキシフエニル）−３−アセトキシ−
５−（２−ジメチルアミノエチル）−２，３−ジヒ
ドロ−１，５−ベンゾチアゼピン−４（5H）−オ
ンを合成する場合には、例えば、２−Ｎ−（２−
ジメチルアミノエチル）アミノチオフエノール
と、前記有機溶媒中にて反応させることにより容
易に達成される。この反応は、本発明の目的化合
物である式（）で表わされる化合物を用いるこ
とにより従来行なわれてきた光学分割の操作を必
要とせず光学活性体を直接得ることを可能にした
ものである。 Next, 2- expressed by the formula () according to the present invention
2-(4-methoxyphenyl)-3-acetoxy- using acetoxy-3-chloro-3-(4-methoxyphenyl)propionic acid alkyl ester
When synthesizing 5-(2-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, for example, 2-N-(2-
This can be easily achieved by reacting dimethylaminoethyl)aminothiophenol in the above-mentioned organic solvent. This reaction makes it possible to directly obtain an optically active substance without the need for the conventional optical resolution operation by using the compound represented by the formula (), which is the target compound of the present invention.
以下に、実施例並びに参考例を挙げて、本発明
を更に具体的に説明する。 The present invention will be explained in more detail below by giving examples and reference examples.
実施例 １
ｐ−メトキシケイ皮酸メチルエステル1.92ｇ
を、クロロホルム30ml、四塩化炭素30mlの混液の
入つた撹拌子付き丸底フラスコに入れて溶解した
後、氷冷下撹拌する。この溶液中へ、四塩化炭素
10mlに塩化クロミル1.55ｇを溶解したものを、撹
拌下に徐々に滴下して加えた後、約１時間反応さ
せた。反応液を２〜３回水洗し、分液濾斗で分離
採集すると褐色のクロロホルム、四塩化炭素層が
得られる。これに無水硫酸ナトリウムを加えて脱
水、濾過後、減圧下にて溶媒を留去すると褐色の
粘稠溶液が1.0ｇ得られた。これに石油エーテル
を加え夾雑物を溶解し、分液漏斗にて石油エーテ
ル層を除去することにより、２−ヒドロキシ−３
−クロロ−３−（４−メトキシフエニル）プロピ
オン酸メチルエステルを得た。Example 1 1.92 g of p-methoxycinnamic acid methyl ester
is dissolved in a round bottom flask with a stir bar containing a mixture of 30 ml of chloroform and 30 ml of carbon tetrachloride, and then stirred under ice-cooling. Into this solution, carbon tetrachloride
A solution of 1.55 g of chromyl chloride in 10 ml was gradually added dropwise while stirring, and the mixture was allowed to react for about 1 hour. The reaction solution is washed with water 2 to 3 times and separated and collected using a separating funnel to obtain a brown chloroform and carbon tetrachloride layer. After dehydration by adding anhydrous sodium sulfate and filtration, the solvent was distilled off under reduced pressure to obtain 1.0 g of a brown viscous solution. By adding petroleum ether to this to dissolve impurities, and removing the petroleum ether layer using a separatory funnel, 2-hydroxy-3
-chloro-3-(4-methoxyphenyl)propionic acid methyl ester was obtained.
引続き、この物質2.5ｇをキシレン50mlに溶解
し、これに塩化アセチル0.78ｇを加え、撹拌下に
加熱還流した。反応終了後、減圧下に溶媒を留去
することにより２−アセトキシ−３−クロロ−３
−（４−メトキシフエニル）プロピオン酸メチル
エチルの褐色粘稠性物質を得た。 Subsequently, 2.5 g of this substance was dissolved in 50 ml of xylene, 0.78 g of acetyl chloride was added thereto, and the mixture was heated to reflux with stirring. After the reaction is completed, the solvent is distilled off under reduced pressure to obtain 2-acetoxy-3-chloro-3.
A brown viscous substance of methylethyl-(4-methoxyphenyl)propionate was obtained.
元素分析値 C13H15O5Clとして
理論値 C54.46％ H5.24％ O27.93％
実測値 C54.37％ H5.22％ O27.89％
赤外吸収スペクトル（KBr錠剤法）は、図１
に示した。 Elemental analysis value C 13 H 15 O 5 As Cl Theoretical value C54.46% H5.24% O27.93% Actual value C54.37% H5.22% O27.89% Infrared absorption spectrum (KBr tablet method) Figure 1
It was shown to.
実施例 ２
実施例１と同様にして得られた２−ヒドロキシ
−３−クロロ−３−（４−メトキシフエニル）プ
ロピオン酸メチルエステル2.0ｇと無水酢酸1.7ｇ
の混合物に氷冷下、乾燥ピリジン0.77ｇを滴下
し、室温で５時間撹拌した。撹拌後、反応混合物
を氷水30mlに注加し、ジエチルエーテルで抽出し
た。エーテル層を水、５％塩酸および飽和食塩水
で洗浄、無水硫酸マグネシウムで乾燥後、エーテ
ルを留去した。得られた黄褐色粘稠性物質をシリ
カゲルカラムクロマトグラフイーに付し、酢酸エ
チル：石油エーテル（１：２）溶出部より、淡黄
色粘稠性物質（淡黄色油状物）である２−アセト
キシ−３−クロロ−３−（４−メトキシフエニル）
プロピオン酸メチルエステル2.0ｇ（収率85.5％）
を得た。このものの物理化学的性質を以下に示
す。Example 2 2.0 g of 2-hydroxy-3-chloro-3-(4-methoxyphenyl)propionic acid methyl ester obtained in the same manner as in Example 1 and 1.7 g of acetic anhydride.
0.77 g of dry pyridine was added dropwise to the mixture under ice cooling, and the mixture was stirred at room temperature for 5 hours. After stirring, the reaction mixture was poured into 30 ml of ice water and extracted with diethyl ether. The ether layer was washed with water, 5% hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and then the ether was distilled off. The obtained yellow-brown viscous substance was subjected to silica gel column chromatography, and from the eluate of ethyl acetate:petroleum ether (1:2), 2-acetoxy, a pale yellow viscous substance (pale yellow oil) was detected. -3-chloro-3-(4-methoxyphenyl)
Propionate methyl ester 2.0g (yield 85.5%)
I got it. The physicochemical properties of this product are shown below.
b.p：160〜161℃（２mmHg） 元素分析値 C13H15O5Clとして 理論値 C54.46％ H5.24％ O27.93％ 実測値 C54.61％ H5.17％ O27.78％ 赤外吸収スペクトル（Neat法）は図２に示した。 bp: 160-161℃ (2mmHg) Elemental analysis value C 13 H 15 O 5 As Cl Theoretical value C54.46% H5.24% O27.93% Actual value C54.61% H5.17% O27.78% Infrared The absorption spectrum (Neat method) is shown in Figure 2.
核磁気共鳴スペクトル（NMR）
CDCl3 δ；
2.05（3H，Ｓ，CH3）
3.82（6H，Ｓ，CH3×２）
5.25（1H，ｄ Ｊ＝６Hz，CH）
5.55（1H，ｄ Ｊ＝６Hz，CH）
6.70〜7.60（4H，ｍ，芳香族Ｈ）
参考例
２−Ｎ−（２−ジメチルアミノエチル）アミノ
チオフエノール1.96ｇをキシレン30mlに溶解し、
これに２−アセトキシ−３−クロロ−３−（４−
メトキシフエニル）プロピオン酸メチルエステル
2.87ｇをキシレン10mlに溶解した液を加え、撹拌
下に約10時間加熱還流を行なつた。この反応液に
塩酸を加えると白色の沈澱が生じ、これを濾過し
て沈澱を採取する。エタノールにより再結晶する
と２−（４−メトキシフエニル）−３−アセトキシ
−５−（２−ジメチルアミノエチル）−２，３−ジ
ヒドロ−１，５−ベンゾチアゼピン−４（5H）−
オン0.8ｇを得た。旋光度〔α〕20 D：＋110〜113゜
このものの赤外吸収スペクトルは、標準品のそ
れと一致した。Nuclear magnetic resonance spectrum (NMR) CDCl 3 δ; 2.05 (3H, S, CH 3 ) 3.82 (6H, S, CH 3 ×2) 5.25 (1H, d J=6Hz, CH) 5.55 (1H, d J=6Hz , CH) 6.70-7.60 (4H, m, aromatic H) Reference example Dissolve 1.96 g of 2-N-(2-dimethylaminoethyl)aminothiophenol in 30 ml of xylene,
This was added to 2-acetoxy-3-chloro-3-(4-
Methoxyphenyl)propionate methyl ester
A solution of 2.87 g dissolved in 10 ml of xylene was added, and the mixture was heated under reflux for about 10 hours while stirring. When hydrochloric acid is added to this reaction solution, a white precipitate is produced, which is collected by filtration. Recrystallization from ethanol yields 2-(4-methoxyphenyl)-3-acetoxy-5-(2-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-
0.8 g of onion was obtained. Optical rotation [α] 20 D : +110 to 113° The infrared absorption spectrum of this product matched that of the standard product.
第１図は本発明生成物（粗製）の赤外線吸収ス
ペクトル（KBr法）であり、第２図は精製品の
赤外線吸収スペクトル（Neat法）である。
Figure 1 shows the infrared absorption spectrum (KBr method) of the product of the present invention (crude), and Figure 2 shows the infrared absorption spectrum (Neat method) of the purified product.
Claims (1)
（４−メトキシフエニル）プロピオン酸アルキル
エステル化合物。 ２ 式（） （式中、Ｒは低級アルキル基を表わす） で表わされるｐ−メトキシケイ皮酸アルキルエス
テルに塩化クロミルを反応させ、式（） （式中、Ｒは前記と同じ） で表わされる２−ヒドロキシ−３−クロロ−３−
（４−メトキシフエニル）プロピオン酸アルキル
エステルを生成し、次いでアセチル化することに
より、式（） （式中、Ｒは前記と同じ） で表わされる２−アセトキシ−３−クロロ−３−
（４−メトキシフエニル）プロピオン酸アルキル
エステルの製造方法。[Claims] 1 Formula () (In the formula, R represents a lower alkyl group) 2-acetoxy-3-chloro-3-
(4-methoxyphenyl)propionic acid alkyl ester compound. 2 formula () (In the formula, R represents a lower alkyl group) Chromyl chloride is reacted with p-methoxycinnamate alkyl ester represented by the formula () (wherein R is the same as above) 2-hydroxy-3-chloro-3-
By generating a (4-methoxyphenyl)propionic acid alkyl ester, followed by acetylation, the formula () (wherein R is the same as above) 2-acetoxy-3-chloro-3-
A method for producing (4-methoxyphenyl)propionic acid alkyl ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21477883A JPS60105646A (en) | 1983-11-15 | 1983-11-15 | Substituted p-methoxyphenyl compound and production thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21477883A JPS60105646A (en) | 1983-11-15 | 1983-11-15 | Substituted p-methoxyphenyl compound and production thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60105646A JPS60105646A (en) | 1985-06-11 |
| JPH041736B2 true JPH041736B2 (en) | 1992-01-14 |
Family
ID=16661374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21477883A Granted JPS60105646A (en) | 1983-11-15 | 1983-11-15 | Substituted p-methoxyphenyl compound and production thereof |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60105646A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989005298A1 (en) * | 1987-11-30 | 1989-06-15 | Ici Australia Operations Proprietary Limited | Process for preparation of aryl substituted propionate derivatives |
| CN111499514A (en) * | 2019-01-31 | 2020-08-07 | 连云港润众制药有限公司 | Preparation method of intermediate of roxasistat |
-
1983
- 1983-11-15 JP JP21477883A patent/JPS60105646A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60105646A (en) | 1985-06-11 |
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