JPS629106B2 - - Google Patents
Info
- Publication number
- JPS629106B2 JPS629106B2 JP2718779A JP2718779A JPS629106B2 JP S629106 B2 JPS629106 B2 JP S629106B2 JP 2718779 A JP2718779 A JP 2718779A JP 2718779 A JP2718779 A JP 2718779A JP S629106 B2 JPS629106 B2 JP S629106B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- cyano
- formula
- ethyl ester
- distilled
- 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 4-isobutylphenyl group Chemical group 0.000 claims description 23
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 claims description 8
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical class OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 5
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- LUOWKRLRGYCJPE-UHFFFAOYSA-N ethyl 2-cyano-2-[4-(2-methylpropyl)phenyl]acetate Chemical compound CCOC(=O)C(C#N)C1=CC=C(CC(C)C)C=C1 LUOWKRLRGYCJPE-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N 2-(6-methoxy-2-naphthalenyl)propanoic acid Chemical compound C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000000126 substance Substances 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
- NLQWCQWHTQUUNU-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)acetonitrile Chemical compound C1=C(CC#N)C=CC2=CC(OC)=CC=C21 NLQWCQWHTQUUNU-UHFFFAOYSA-N 0.000 description 1
- INYXZKUEDMCFSU-UHFFFAOYSA-N 2-[4-(2-methylpropyl)phenyl]acetonitrile Chemical compound CC(C)CC1=CC=C(CC#N)C=C1 INYXZKUEDMCFSU-UHFFFAOYSA-N 0.000 description 1
- GDDISYJDFUYFAW-UHFFFAOYSA-N 2-cyano-2-(6-methoxynaphthalen-2-yl)propanoic acid Chemical compound C1=C(C(C)(C#N)C(O)=O)C=CC2=CC(OC)=CC=C21 GDDISYJDFUYFAW-UHFFFAOYSA-N 0.000 description 1
- JDEFPFLTCXIVDH-UHFFFAOYSA-N 2-cyanopropanoic acid Chemical class N#CC(C)C(O)=O JDEFPFLTCXIVDH-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000008366 benzophenones Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- VGLCBSOALKYKJU-UHFFFAOYSA-N ethyl 2-cyano-2-(3-phenoxyphenyl)acetate Chemical compound CCOC(=O)C(C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 VGLCBSOALKYKJU-UHFFFAOYSA-N 0.000 description 1
- RFALKMQNBPHELA-UHFFFAOYSA-N ethyl 2-cyano-2-(3-phenoxyphenyl)propanoate Chemical compound CCOC(=O)C(C)(C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 RFALKMQNBPHELA-UHFFFAOYSA-N 0.000 description 1
- UBLGKELIZNZYPR-UHFFFAOYSA-N ethyl 2-cyano-2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound CCOC(=O)C(C)(C#N)C1=CC=C(CC(C)C)C=C1 UBLGKELIZNZYPR-UHFFFAOYSA-N 0.000 description 1
- RDJGLLICXDHJDY-UHFFFAOYSA-N fenoprofen Chemical compound OC(=O)C(C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229960003101 pranoprofen Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
（式中、R1は４−イソブチルフエニル基、３
−ベンゾイルフエニル基、６−メトキシ−２−ナ
フチル基、２−フルオロ−４−ビフエニリル基、
３−フエノキシフエニル基、5H−〔１〕ベンゾピ
ラノ〔２，３−ｂ〕ピリジン−７−イル基を意味
し、R2は炭素数１ないし３の低級アルキル基を
意味する。）で表わされるα−シアノプロピオン
酸エステル誘導体の新規な製造法に関するもので
ある。[Detailed description of the invention] (In the formula, R 1 is a 4-isobutylphenyl group, 3
-benzoylphenyl group, 6-methoxy-2-naphthyl group, 2-fluoro-4-biphenylyl group,
It means a 3-phenoxyphenyl group or a 5H-[1]benzopyrano[2,3-b]pyridin-7-yl group, and R2 means a lower alkyl group having 1 to 3 carbon atoms. ) The present invention relates to a novel method for producing an α-cyanopropionic acid ester derivative represented by the following.
更に詳しくは一般式（）
（式中、R1及びR2は前記と同じ意味を有す
る）で表わされるシアノ酢酸エステル誘導体に式
（）
で表わされるＮ，Ｎ−ジメチルホルムアミドジメ
チルアセタールを反応させることを特徴とする一
般式（）
（式中、R1及びR2は前記と同じ意味を有す
る）で表わされるα−シアノプロピオン酸エステ
ル誘導体の製造法に関するものである。 For more details, see the general formula () (In the formula, R 1 and R 2 have the same meanings as above.) General formula () characterized by reacting N,N-dimethylformamide dimethyl acetal represented by The present invention relates to a method for producing an α-cyanopropionic acid ester derivative represented by the formula (wherein R 1 and R 2 have the same meanings as above).
本発明の製造法によつて得られる前記一般式
（）で表わされる目的化合物は、顕著な抗炎症
作用、鎮痛作用及び解熱作用を有する４−イソブ
チルフエニルプロピオン酸〔一般名：イブプロフ
エン（米国特許：第3228831号及び第3385886
号）〕、３−ベンゾイルフエニルプロピオン酸〔一
般名：ケトプロフエン（米国特許：第3641127
号）〕、２−（６−メトキシ−２−ナフチル）プロ
ピオン酸〔一般名：ナプロキセン（米国特許：第
3637767号）〕、２−（２−フルオロ−４−ビフエニ
ル）プロピオン酸〔一般名：フルルビプロフエン
（米国特許：第3755427号）〕、２−（３−フエノキ
シフエニル）プロピオン酸〔一般名：フエノプロ
フエン（米国特許：第3600437号）〕、２−（5H−
〔１〕−ベンゾピラノ〔２，３−ｂ〕ピリジン−７
−イル）プロピオン酸〔一般名：プラノプロフエ
ン（特公昭51−6157号公報）〕等の医薬品中間体
として産業上非常に有用な化合物である。 The target compound represented by the general formula () obtained by the production method of the present invention is 4-isobutylphenylpropionic acid [generic name: ibuprofen (U.S. patent : No. 3228831 and No. 3385886
No.)], 3-benzoylphenylpropionic acid [generic name: ketoprofen (US Patent: No. 3641127)
2-(6-methoxy-2-naphthyl)propionic acid [generic name: naproxen (U.S. patent: No.
3637767)], 2-(2-fluoro-4-biphenyl)propionic acid [generic name: flurbiprofen (U.S. Patent No. 3755427)], 2-(3-phenoxyphenyl)propionic acid [general Name: Fuenoprofen (US Patent: No. 3600437)], 2-(5H-
[1]-benzopyrano[2,3-b]pyridine-7
-yl) propionic acid [generic name: pranoprofen (Japanese Patent Publication No. 51-6157)], it is a very useful compound industrially as a pharmaceutical intermediate.
従来、前記一般式（）で表わされるシアノ酢
酸エステル誘導体のＣ−メチル化による前記一般
式（）で表わされるα−シアノプロピオン酸エ
ステル誘導体の製造法としては、特公昭45−
19287号公報、特公昭51−45586号公報及び特開昭
53−116352号公報等に見られるように、最初に金
属ナトリウム、水素化ナトリウム等でシアノ酢酸
エステル誘導体のアルカリ金属誘導体を製造し、
次いでエタノール等の有機溶媒中においてヨウ化
メチル、臭化メチル等のメチルハライド化合物又
はジメチル硫酸等と反応させることにより得てい
る。しかし乍ら、これら従来法は危険性の高い金
属ナトリウムや水素ナトリウムを用いるためにそ
の取り扱いに十分な注意を必要とし、又、ヨウ化
メチル（沸点：41〜43℃）等のメチルハライド化
合物は低沸点のため揮発性が非常に高くその取り
扱いや作業環境等の作業性の面で問題が多く、労
働衛生上問題があり、又、反応収量の点でも必ず
しも満足できるものではなかつた。 Conventionally, as a method for producing an α-cyanopropionate derivative represented by the general formula () by C-methylation of a cyanoacetate derivative represented by the general formula (), there is a method disclosed in Japanese Patent Publication No. 1973-
Publication No. 19287, Japanese Patent Publication No. 51-45586, and Japanese Patent Application Publication No. 1987-45586
As seen in Publication No. 53-116352, etc., first, an alkali metal derivative of a cyanoacetate derivative is produced using metallic sodium, sodium hydride, etc.
Then, it is obtained by reacting with a methyl halide compound such as methyl iodide or methyl bromide, or dimethyl sulfate in an organic solvent such as ethanol. However, these conventional methods require great care when handling highly dangerous metal sodium and sodium hydride, and methyl halide compounds such as methyl iodide (boiling point: 41-43°C) are Due to its low boiling point, it has very high volatility, which causes many problems in terms of handling and workability such as working environment, causing problems in terms of occupational health, and the reaction yield is not always satisfactory.
そこで本発明者等はシアノ酢酸エステル誘導体
のＣ−メチル化剤の検討について鋭意研究を重ね
た結果、テトラヒドロフラン中、Ｎ，Ｎ−ジメチ
ルホルムアミドジメチルアセタールと反応させる
と定量的にＣ−メチル化反応が進行するという新
知見を見い出した。又、Ｎ，Ｎ−ジメチルホルム
アミドジメチルアセタールを使用すると上記の問
題点をすべて解決すると共に作業操作が簡略でき
るため、企業上有用な製造法であることを見出し
本発明を完成したのである。 Therefore, the present inventors have conducted extensive research on C-methylating agents for cyanoacetic acid ester derivatives, and have found that a quantitative C-methylation reaction is observed when the cyanoacetate derivatives are reacted with N,N-dimethylformamide dimethyl acetal in tetrahydrofuran. We discovered new knowledge that the process progresses. They also discovered that the use of N,N-dimethylformamide dimethyl acetal solves all of the above-mentioned problems and simplifies work operations, making it an industrially useful manufacturing method and has completed the present invention.
尚、本発明の反応は一般式（）のシアノ酢酸
エステル誘導体とその１〜２倍モルのＮ，Ｎ−ジ
メチルホルムアミドジメチルアセタールをテトラ
ヒドロフラン、ジオキサン、塩化メチレン、ベン
ゼン、ジメチルホルムアミド等の不活性有機溶媒
中、50〜100℃で１〜15時間反応させるだけで十
分である。 In the reaction of the present invention, the cyanoacetate derivative of general formula () and 1 to 2 times the mole of N,N-dimethylformamide dimethyl acetal are mixed in an inert organic solvent such as tetrahydrofuran, dioxane, methylene chloride, benzene, dimethylformamide, etc. A reaction time of 1 to 15 hours at 50 to 100°C is sufficient.
以下に参考例及び本発明の実施例を示す。 Reference examples and examples of the present invention are shown below.
参考例 １
６−メトキシ−２−ナフタレンアセトニトリル
2.0ｇと炭酸ジエチル5.9ｇを混合し、更に冷却下
の状態にてエチラート0.9ｇを加えて30分間撹拌
する。次いで85〜90℃にて４時間加熱撹拌する。
反応終了後塩化メチレンにて抽出し水洗する。塩
化メチレン層を脱水剤で脱水後、塩化メチレン及
び過剰の炭酸ジエチルを減圧下に留去し、更に精
製すると融点45〜46℃のα−シアノ−（６−メト
キシ−２−ナフチル）酢酸エチルエステル2.5ｇ
を得た。Reference example 1 6-methoxy-2-naphthaleneacetonitrile
Mix 2.0 g of diethyl carbonate and 5.9 g of diethyl carbonate, add 0.9 g of ethylate under cooling, and stir for 30 minutes. Then, the mixture is heated and stirred at 85 to 90°C for 4 hours.
After the reaction is complete, extract with methylene chloride and wash with water. After dehydrating the methylene chloride layer with a dehydrating agent, methylene chloride and excess diethyl carbonate are distilled off under reduced pressure, and further purification yields α-cyano-(6-methoxy-2-naphthyl)acetic acid ethyl ester with a melting point of 45-46°C. 2.5g
I got it.
参考例 ２
４−イソブチルフエニルアセトニトリル3.5ｇ
をエタノール30mlに溶解し、更に冷却下エチラー
ト1.6ｇを加え室温にて30分間撹拌する。次に減
圧下にエタノールを留去し、残渣に炭酸ジエチル
11.8ｇを加え油浴中80〜85℃にて３時間撹拌す
る。反応終了後、塩化メチレンにて抽出し水洗す
る。次に塩化メチレン層を脱水剤にて脱水後、塩
化メチレン及び過剰の炭酸ジエチルを留去すると
油状物が得られる。Reference example 2 4-isobutylphenylacetonitrile 3.5g
Dissolve in 30 ml of ethanol, add 1.6 g of ethylate under cooling, and stir at room temperature for 30 minutes. Next, ethanol was distilled off under reduced pressure, and diethyl carbonate was added to the residue.
Add 11.8g and stir in an oil bath at 80-85°C for 3 hours. After the reaction is complete, extract with methylene chloride and wash with water. Next, the methylene chloride layer is dehydrated using a dehydrating agent, and then methylene chloride and excess diethyl carbonate are distilled off to obtain an oily substance.
更に減圧蒸留により精製すると沸点92〜95℃
（0.15mmHg）のα−シアノ−（４−イソブチルフ
エニル）酢酸エチルエステル3.9ｇを得た。 When further purified by vacuum distillation, the boiling point is 92-95℃.
(0.15 mmHg) 3.9 g of α-cyano-(4-isobutylphenyl)acetic acid ethyl ester was obtained.
実施例 １
参考例１の方法で得られたα−シアノ（６−メ
トキシ−２−ナフチル）酢酸エチルエステル３ｇ
を乾燥したテトラヒドロフラン50mlに溶解した中
にＮ，Ｎ−ジメチルホルムアミドジメチルアセタ
ール2.5ｇを加え還流下に15時間加熱した。反応
終了後、溶媒を減圧下に留去し残渣を減圧下に蒸
留すると無色油状の２−シアノ−２−（６−メト
キシ−２−ナフチル）プロピオン酸エステル2.8
ｇを得た。Example 1 3 g of α-cyano(6-methoxy-2-naphthyl)acetic acid ethyl ester obtained by the method of Reference Example 1
was dissolved in 50 ml of dry tetrahydrofuran, 2.5 g of N,N-dimethylformamide dimethyl acetal was added thereto, and the mixture was heated under reflux for 15 hours. After the reaction is complete, the solvent is distilled off under reduced pressure and the residue is distilled under reduced pressure to obtain colorless oily 2-cyano-2-(6-methoxy-2-naphthyl)propionic acid ester 2.8
I got g.
この物質の沸点は165〜170℃（0.25mmHg）で
あつた。又、この物質のマススペクトル親イオン
（ｍ／ｅ）は283を示した。 The boiling point of this material was 165-170°C (0.25mmHg). Moreover, the mass spectrum parent ion (m/e) of this substance was 283.
実施例 ２
α−シアノ−（３−ベンゾイルフエニル）酢酸
エチルエステル〔特公昭45−19287号公報記載の
方法に準じて製造〕2.9ｇとＮ，Ｎ−ジメチルホ
ルムアミドジメチルアセタール2.4ｇの混合物を
70mlのテトラヒドロフラン中で５時間還流した。
反応終了後、溶媒を減圧下に留去し残渣をシリカ
ゲルを充填したカラムに吸着させ、イソプロピル
エーテルで展開し、溶出部の溶媒を留去して無色
油状の２−シアノ−２−（３−ベンゾイルフエニ
ル）プロピオン酸エチルエステル2.9ｇを得た。Example 2 A mixture of 2.9 g of α-cyano-(3-benzoylphenyl) acetic acid ethyl ester [manufactured according to the method described in Japanese Patent Publication No. 45-19287] and 2.4 g of N,N-dimethylformamide dimethyl acetal was
The mixture was refluxed in 70 ml of tetrahydrofuran for 5 hours.
After the reaction, the solvent was distilled off under reduced pressure, the residue was adsorbed on a column packed with silica gel, developed with isopropyl ether, and the solvent in the eluate was distilled off to give 2-cyano-2-(3- 2.9 g of benzoyl phenyl) propionic acid ethyl ester was obtained.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は307を示した。 The parent ion in the mass spectrum of this material (m/
e) showed 307.
実施例 ３
参考例２の方法で得られたα−シアノ−（４−
イソブチルフエニル）酢酸エチルエステル2.3ｇ
とＮ，Ｎ−ジメチルホルムアミドジメチルアセタ
ール2.4ｇの混合物を50mlのジメチルホルムアミ
ド中で80℃にて４時間加熱した。反応終了後、溶
媒を減圧下に留去し残渣を減圧下に蒸留すると無
色油状の２−シアノ−２−（４−イソブチルフエ
ニル）プロピオン酸エステル2.3ｇを得た。Example 3 α-cyano-(4-
Isobutylphenyl) acetic acid ethyl ester 2.3g
A mixture of 2.4 g of dimethylacetal and N,N-dimethylformamide was heated in 50 ml of dimethylformamide at 80° C. for 4 hours. After the reaction was completed, the solvent was distilled off under reduced pressure and the residue was distilled under reduced pressure to obtain 2.3 g of 2-cyano-2-(4-isobutylphenyl)propionic acid ester as a colorless oil.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は247を示した。 The parent ion in the mass spectrum of this material (m/
e) showed 247.
実施例 ４
参考例２の方法で得られたα−シアノ−（４−
イソブチルフエニル）酢酸エチルエステル2.3ｇ
とＮ，Ｎ−ジメチルホルムアミドジメチルアセタ
ール2.4ｇの混合物を50mlのジメチルホルムアミ
ド中で80℃にて４時間加熱した。反応終了後、溶
媒を減圧下に留去し残渣を減圧下に蒸留すると無
色油状の２−シアノ−２−（４−イソブチルフエ
ニル）プロピオン酸エチルエステル2.3ｇを得
た。Example 4 α-cyano-(4-
Isobutylphenyl) acetic acid ethyl ester 2.3g
A mixture of 2.4 g of dimethylacetal and N,N-dimethylformamide was heated in 50 ml of dimethylformamide at 80° C. for 4 hours. After the reaction was completed, the solvent was distilled off under reduced pressure and the residue was distilled under reduced pressure to obtain 2.3 g of 2-cyano-2-(4-isobutylphenyl)propionic acid ethyl ester as a colorless oil.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は247を示した。 Parent ion (m/
e) showed 247.
実施例 ４
α−シアノ−（２−フルオロ−４−ビフエニ
ル）酢酸エチルエステル〔特開昭53−116352号公
報記載の方法に準じて製造〕2.8ｇとＮ，Ｎ−ジ
メチルホルムアミドジメチルアセタール2.4ｇの
混合物を50mlのジメチルホルムアミド中で80〜85
℃にて５時間加熱した。反応終了後、溶媒を減圧
下に留去し、残留物を更に減圧蒸留して精製する
と無色油状の２−シアノ−２−（２−フルオロ−
４−ビフエニル）プロピオン酸エチルエステル
2.75ｇを得た。Example 4 2.8 g of α-cyano-(2-fluoro-4-biphenyl)acetic acid ethyl ester [produced according to the method described in JP-A-53-116352] and 2.4 g of N,N-dimethylformamide dimethyl acetal. Mix 80-85 in 50ml dimethylformamide
It was heated at ℃ for 5 hours. After the reaction is complete, the solvent is distilled off under reduced pressure, and the residue is purified by further distillation under reduced pressure to obtain 2-cyano-2-(2-fluoro-
4-biphenyl)propionic acid ethyl ester
2.75g was obtained.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は297を示した。 The parent ion in the mass spectrum of this material (m/
e) showed 297.
実施例 ５
２−シアノ−２−（5H−〔１〕ベンゾピラノ
〔２，３−ｂ〕ピリジン−７−イル）酢酸エチル
エステル〔特開昭49−93398号公報記載の方法に
準じて製造〕2.9ｇとＮ，Ｎ−ジメチルホルムア
ミドジメチルアセタール2.4ｇの混合物を50mlの
ジメチルホルムアミド中で80〜85℃にて６時間加
熱した。反応終了後、溶媒を減圧下に留去し、残
留物を更に減圧蒸留して精製すると無色油状の２
−シアノ−２−（5H−〔１〕ベンゾピラノ〔２，
３−ｂ〕ピリジン−７−イル）プロピオン酸エチ
ルエステル2.8ｇを得た。Example 5 2-cyano-2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl)acetic acid ethyl ester [manufactured according to the method described in JP-A-49-93398] 2.9 A mixture of 2.4 g of dimethylacetal and N,N-dimethylformamide was heated in 50 ml of dimethylformamide at 80-85°C for 6 hours. After the reaction is completed, the solvent is distilled off under reduced pressure, and the residue is further purified by distillation under reduced pressure to obtain colorless oil 2.
-cyano-2-(5H-[1]benzopyrano[2,
3-b] pyridin-7-yl)propionic acid ethyl ester (2.8 g) was obtained.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は308を示した。 The parent ion in the mass spectrum of this material (m/
e) showed 308.
実施例 ６
２−シアノ−（３−フエノキシフエニル）酢酸
エチルエステル〔特公昭51−45586号公報記載の
方法に準じて製造〕を原料として用い、実施例１
〜５の方法に準じて、無色油状物の２−シアノ−
２−（３−フエノキシフエニル）プロピオン酸エ
チルエステルを合成した。Example 6 Using 2-cyano-(3-phenoxyphenyl)acetic acid ethyl ester [manufactured according to the method described in Japanese Patent Publication No. 51-45586] as a raw material, Example 1
According to the method of ~5, 2-cyano-
2-(3-phenoxyphenyl)propionic acid ethyl ester was synthesized.
この物質のマススペクトルの親イオン（ｍ／
ｅ）は295を示した。 The parent ion in the mass spectrum of this material (m/
e) showed 295.
Claims (1)
−ベンゾイルフエニル基、６−メトキシ−２−ナ
フチル基、２−フルオロ−４−ビフエニリル基、
３−フエノキシフエニル基、5H−〔１〕ベンゾピ
ラノ〔２，３−ｂ〕ピリジン−７−イル基を意味
し、R2は炭素数１ないし３の低級アルキル基を
意味する。）で表わされるシアノ酢酸エステル誘
導体に式（） で表わされるＮ，Ｎ−ジメチルホルムアミドジメ
チルアセタールを反応させることを特徴とする一
般式（） （式中、R1及びR2は前記と同じ意味を有す
る）で表わされるα−シアノプロピオン酸エステ
ル誘導体の製造法。[Claims] 1 General formula () (In the formula, R 1 is a 4-isobutylphenyl group, 3
-benzoylphenyl group, 6-methoxy-2-naphthyl group, 2-fluoro-4-biphenylyl group,
It means a 3-phenoxyphenyl group or a 5H-[1]benzopyrano[2,3-b]pyridin-7-yl group, and R2 means a lower alkyl group having 1 to 3 carbon atoms. ) to the cyanoacetate derivative represented by the formula () General formula () characterized by reacting N,N-dimethylformamide dimethyl acetal represented by A method for producing an α-cyanopropionic acid ester derivative represented by the formula (wherein R 1 and R 2 have the same meanings as above).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2718779A JPS55118452A (en) | 1979-03-06 | 1979-03-06 | Production of alpha-cyanopropionic ester derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2718779A JPS55118452A (en) | 1979-03-06 | 1979-03-06 | Production of alpha-cyanopropionic ester derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55118452A JPS55118452A (en) | 1980-09-11 |
| JPS629106B2 true JPS629106B2 (en) | 1987-02-26 |
Family
ID=12214065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2718779A Granted JPS55118452A (en) | 1979-03-06 | 1979-03-06 | Production of alpha-cyanopropionic ester derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55118452A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ218717A (en) * | 1985-12-20 | 1989-10-27 | Wisconsin Alumni Res Found | Process for preparing an (s)alpha-methylarylacetic acid from a mixture of (r) and (s)-#a#-methylarylacetic acid esters |
-
1979
- 1979-03-06 JP JP2718779A patent/JPS55118452A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55118452A (en) | 1980-09-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4881298B2 (en) | Method for producing indenol ester or ether | |
| JPH09208516A (en) | Production of alpha, beta-unsaturated organic carboxylic acid | |
| KR950003120B1 (en) | Improved process for preparing 5-(2,5-dimethyl phenoxy)-2,2-dimetheyl pentanoic acid | |
| JPS629106B2 (en) | ||
| JP2020520974A (en) | Method for preparing substituted phenylacetic acid derivative | |
| JPH01156965A (en) | Thiohydantoin compound | |
| US5041640A (en) | Process for mono-, di-, trisubstituted acetic acids | |
| EP0009306B1 (en) | Anti-arthritic hydroxyacetic acid derivatives, pharmaceutical compositions thereof, and processes for their manufacture | |
| US5095136A (en) | Method for preparing isoprenoid cyclopropane 1,1-dicarboxylates and derivatives thereof and novel intermediates | |
| US4927945A (en) | Process for preparing diphenyl ethers | |
| US3116324A (en) | Preparation of ortho-phenethylbenzoic acids by hydrogenation of 3-benzalphthalides | |
| Berthelot et al. | Solvent incorporation in bromination of alkynes with tetrabutylammonium tribromide in methanol | |
| JP3779615B2 (en) | Process for producing 5- and / or 6-substituted-2-hydroxybenzoic acid esters | |
| US4203907A (en) | Process for preparing a furanic compound | |
| HU196778B (en) | Process for production of new acetilene furane derivatives | |
| JPH04243888A (en) | Imidazo(1,2-a)pyridine derivative, production thereof and alpha-haloketone derivative as intermediate | |
| JP2710837B2 (en) | Method for producing optically active β-hydroxythioester | |
| JPS6328908B2 (en) | ||
| FI66344C (en) | PROCEDURE FOR FRAMSTATION OF AV D-2- (6-METOXY-2-NAPHTHYL) PROPIONYRA | |
| KR100629770B1 (en) | Purin derivatives and synthesizing method thereof | |
| JPH0234943B2 (en) | ||
| JPH0761952A (en) | Production of halomethylbiphenylcarboxylic acid ester derivative | |
| JPH0216750B2 (en) | ||
| JPH11171799A (en) | Production of biphenyl derivative having active substituent group | |
| JPH035381B2 (en) |