JPH0369908B2 - - Google Patents
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- Publication number
- JPH0369908B2 JPH0369908B2 JP7222589A JP7222589A JPH0369908B2 JP H0369908 B2 JPH0369908 B2 JP H0369908B2 JP 7222589 A JP7222589 A JP 7222589A JP 7222589 A JP7222589 A JP 7222589A JP H0369908 B2 JPH0369908 B2 JP H0369908B2
- Authority
- JP
- Japan
- Prior art keywords
- cis
- compound
- present
- added
- formula
- 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.)
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- 150000001875 compounds Chemical class 0.000 claims description 12
- AKAJVSSDORNOIX-SYDPRGILSA-N (3s,5r)-3,5-dibromocyclopentene Chemical compound Br[C@H]1C[C@@H](Br)C=C1 AKAJVSSDORNOIX-SYDPRGILSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000001979 organolithium group Chemical group 0.000 claims description 4
- HYGDHSYCSJKRFX-UHFFFAOYSA-N 1h-cyclopenta[b][1]benzofuran Chemical compound O1C2=CC=CC=C2C2=C1C=CC2 HYGDHSYCSJKRFX-UHFFFAOYSA-N 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 4
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 4
- -1 etc. are used Chemical compound 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004210 ether based solvent Substances 0.000 description 3
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OJDPRKDUDHDHLL-CALCHBBNSA-N [(1r,4s)-4-phenoxycyclopent-2-en-1-yl]oxybenzene Chemical class O([C@@H]1C[C@@H](C=C1)OC=1C=CC=CC=1)C1=CC=CC=C1 OJDPRKDUDHDHLL-CALCHBBNSA-N 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
- 150000001907 coumarones Chemical class 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QIRNGVVZBINFMX-UHFFFAOYSA-N 2-allylphenol Chemical compound OC1=CC=CC=C1CC=C QIRNGVVZBINFMX-UHFFFAOYSA-N 0.000 description 1
- SBRRDWKWIGRYCN-UHFFFAOYSA-N 2h-cyclopenta[g][1]benzofuran Chemical class C1=CC2=CCOC2=C2C=CC=C21 SBRRDWKWIGRYCN-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- CDGKAKGXZKGAIU-UHFFFAOYSA-N cyclopentene;methanol Chemical compound OC.C1CC=CC1 CDGKAKGXZKGAIU-UHFFFAOYSA-N 0.000 description 1
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 1
- BBGKDYHZQOSNMU-UHFFFAOYSA-N dicyclohexano-18-crown-6 Chemical compound O1CCOCCOC2CCCCC2OCCOCCOC2CCCCC21 BBGKDYHZQOSNMU-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
Landscapes
- Furan Compounds (AREA)
Description
【発明の詳細な説明】
［産業の利用分野］
本発明は、医薬品、特に抗血栓剤として有用で
ある５，６，７−トリノル−４，８−インターｍ
−フエニレンPGI2誘導体の製造原料として用い
られる3a，8b−シス−ジヒドロ−3H−シクロペ
ンタ［ｂ］ベンゾフランの製造方法に関するもの
である。Detailed Description of the Invention [Field of Industrial Application] The present invention provides 5,6,7-trinor-4,8-interm which is useful as a pharmaceutical, especially an antithrombotic agent.
The present invention relates to a method for producing 3a,8b-cis-dihydro-3H-cyclopenta[b]benzofuran, which is used as a raw material for producing -phenylene PGI 2 derivatives.
［従来の技術］
本発明の目的化合物である式（）
のシクロペンタ［ｂ］ベンゾフラン誘導体の製造
方法としては、アリルフエノールをパラジウム
（）を用いて環化させる方法が知られている。
（T.Hosokawa，J.Org.Chem.，43，（14）（1978）
p2752−2757，T.Hosokawa，J.C.S.Chem.
Comm.，（16）（1978）p687−688）。[Prior art] Formula () which is the object compound of the present invention As a method for producing the cyclopenta[b]benzofuran derivative, a method is known in which allylphenol is cyclized using palladium ().
(T.Hosokawa, J.Org.Chem., 43 , (14) (1978)
p2752−2757, T.Hosokawa, JCSChem.
Comm., (16) (1978) p687-688).
［発明が解決しようとする課題］
しかしながら、前述の方法は下記式（）
の化合物が主生成物であり、本発明の目的化合物
（）の収率は10％程度にすぎない。[Problem to be solved by the invention] However, the above-mentioned method uses the following formula () The compound (2) is the main product, and the yield of the target compound (2) of the present invention is only about 10%.
また、式（）、（）の異性体混合物として生
成され、本発明化合物（）を単離することは困
難である。 In addition, it is produced as an isomer mixture of formulas () and (), and it is difficult to isolate the compound () of the present invention.
本発明の目的は、かかる従来技術の欠点を鑑
み、本発明化合物（）の工業的に有用な製造方
法を提供することにある。 An object of the present invention is to provide an industrially useful method for producing the compound () of the present invention in view of the drawbacks of the prior art.
［課題を解決するための手段］
上述の目的を達成するために、本発明は以下の
構成を有する。[Means for Solving the Problems] In order to achieve the above object, the present invention has the following configuration.
すなわち、本発明は下記一般式（）
（ＭはNaあるいはＫを表す）
で示される化合物を、３，５−シスジブロモシク
ロペンテンと反応させ、式（）
で示される化合物とし、
次いで、有機リチウム試薬と反応させることを
特徴とする式（）
で示されるシクロペンタ［ｂ］ベンゾフランの製
造方法である。 That is, the present invention is based on the following general formula () (M represents Na or K) is reacted with 3,5-cis dibromocyclopentene to form the formula () A compound represented by the formula (), which is then reacted with an organolithium reagent. This is a method for producing cyclopenta[b]benzofuran shown by
本発明のシクロペンタベンゾフラン誘導体
（）は、式（）
（ＭはNaあるいはＫを表す）
で示されるフエノール誘導体および３，５−シス
ジブロモ−シクロペンテン（W.G.Yowng，H.K.
Hall，Jr.and S.Winstein，J.Awer，Chem.
Soc.，78，4338（1956））を原料として、次の２工
程で合成される。 The cyclopentabenzofuran derivative () of the present invention has the formula () (M represents Na or K) and 3,5-cis dibromo-cyclopentene (WG Young, HK
Hall, Jr. and S. Winstein, J. Awer, Chem.
Soc., 78, 4338 (1956)) as a raw material, it is synthesized in the following two steps.
工程Ａ−１は、フエノール誘導体（）を３，
５−シスジブロモシクロペンテンと反応させるこ
とによつて、３，５−シスビスフエノキシシクロ
ペンテン誘導体（）を得る工程である。すなわ
ち、化合物（）（Ｍは前記定義に同じ）を溶媒
に溶かして相間移動触媒を加え、３，５−シスジ
ブロモシクロペンテンと反応させるか、またはシ
クロペンタジエンを溶媒に溶かし、臭素と反応さ
せたものを単離することなしに、前記（）の溶
液と反応させることによつて（）が得られる。 In step A-1, the phenol derivative () is added to 3,
This is a step of obtaining a 3,5-cisbisphenoxycyclopentene derivative () by reacting with 5-cisdibromocyclopentene. That is, compound () (M is the same as defined above) is dissolved in a solvent, a phase transfer catalyst is added, and the mixture is reacted with 3,5-cis dibromocyclopentene, or cyclopentadiene is dissolved in a solvent and reacted with bromine. By reacting with a solution of the above () without isolating it, () is obtained.
溶媒としては、ジエチルエーテル、テトラヒド
ロフラン、１，２−ジメトキシエタン、ジオキサ
ン等のエーテル系溶媒か、またはトルエン、ベン
ゼン等の芳香族炭化水素系溶媒が用いられるが、
なかでもエーテル系溶媒が好ましく、特に１，２
−ジメトキシエタンおよびテトラヒドロフランが
好ましい。 As the solvent, ether solvents such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, and dioxane, or aromatic hydrocarbon solvents such as toluene and benzene are used.
Among them, ether solvents are preferred, especially 1,2
-dimethoxyethane and tetrahydrofuran are preferred.
シクロペンタジエンと臭素の反応に用いられる
溶媒としては、ジクロロメタン、クロロホルム、
四塩化炭素等のハロゲン化炭化水素系溶媒が用い
られ、なかでもジクロロメタンが好ましい。 Solvents used for the reaction of cyclopentadiene and bromine include dichloromethane, chloroform,
A halogenated hydrocarbon solvent such as carbon tetrachloride is used, and dichloromethane is particularly preferred.
相間移動触媒としては、文献（W.P.Weber
and G.W.Gokel，田伏岩夫、西谷孝子共訳、相
間移動触媒，p309，化学同人）に記載されたも
のがあげられるが、なかでもジシクロヘキシル−
18−クラウン−６、ジベンゾ−18−クラウン−
６、臭化テトラブチルアンモニウム、18−クラウ
ン−６等が用いられ、通常、18−クラウン−６が
用いられる。しかし、これらに限られるものでは
ない。 As a phase transfer catalyst, the literature (WPWeber
and GWGokel, co-translated by Iwao Tabuse and Takako Nishitani, Phase Transfer Catalyst, p309, Kagaku Doujin), among which dicyclohexyl-
18-crown-6, dibenzo-18-crown-
6, tetrabutylammonium bromide, 18-crown-6, etc. are used, and 18-crown-6 is usually used. However, it is not limited to these.
反応温度としては−78〜50℃が好ましく、なか
でも−30〜30℃が好ましい。反応時間は５〜120
時間が用いられ、通常は12〜36時間が用いられ
る。化合物（）は、反応混合物中に結晶として
析出し、反応終了後は過し、水、ジエチル、エ
ーテル、石油エーテルで洗浄するのみで、ほぼ純
品が得られる。 The reaction temperature is preferably -78 to 50°C, particularly preferably -30 to 30°C. Reaction time is 5-120
time is used, typically 12 to 36 hours. Compound () precipitates as crystals in the reaction mixture, and after the reaction is complete, a nearly pure product can be obtained by simply filtering and washing with water, diethyl, ether, or petroleum ether.
工程Ａ−２は、分子内環化反応によりベンゾフ
ラン誘導体（）を得る工程である。すなわち、
３，５−シスビスフエノキシシクロペンテン誘導
体（）を溶媒に溶解または懸濁し、有機リチウ
ム試薬と反応させ、ハロゲン金属交換を行つた
後、分子内環化させることによつてベンゾフラン
誘導体（）を得る工程である。 Step A-2 is a step of obtaining a benzofuran derivative () by an intramolecular cyclization reaction. That is,
The benzofuran derivative () is obtained by dissolving or suspending the 3,5-cisbisphenoxycyclopentene derivative () in a solvent, reacting it with an organolithium reagent, performing halogen metal exchange, and then intramolecular cyclization. This is the process of obtaining
用いる溶媒としては、ジエチルエーテル、テト
ラヒドロフラン、１，２−ジメトキシエタン、ジ
オキサン等のエーテル系溶媒が通常用いられる
が、なかでもテトラヒドロフランが特に好まし
い。 As the solvent used, ether solvents such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, and dioxane are usually used, and among them, tetrahydrofuran is particularly preferred.
有機リチウム試薬としては、通常アルキルリチ
ウムまたはアリールリチウムが用いられ、特に好
ましくは、メチルリチウム、ｎ−ブチルリチウ
ム、フエニルリチウムが用いられる。 As the organolithium reagent, alkyllithium or aryllithium is usually used, and methyllithium, n-butyllithium, and phenyllithium are particularly preferably used.
ハロゲン−金属交換の反応温度および時間とし
ては、−78〜100℃で0.5分〜10時間が用いられ、
なかでも−78〜40℃で0.5分〜１時間が好ましい。
分子内環化の反応温度および時間としては、−78
〜100℃で１分〜10時間が用いられ、なかでも−
40〜40℃で５分〜４時間が好ましい。 The reaction temperature and time for halogen-metal exchange are -78 to 100°C for 0.5 minutes to 10 hours,
Among these, 0.5 minutes to 1 hour at -78 to 40°C is preferable.
The reaction temperature and time for intramolecular cyclization are -78
~100℃ for 1 minute to 10 hours, especially −
Preferably, the temperature is 40 to 40°C for 5 minutes to 4 hours.
（）の単離方法としては、蒸留、シリカゲル
カラムクロマトグラフイーが通常用いられる。 Distillation and silica gel column chromatography are commonly used to isolate ().
［実施例］
以下に本発明の実施例について述べる。なお以
下の略号を用いた。[Example] Examples of the present invention will be described below. The following abbreviations were used.
IR：赤外吸収スペクトル（主要なバンドのみ
記載）
NMR：プロトン核磁気共鳴スペクトル
Mass：質量スペクトル
実施例 １
３，５−シス−ビス（ｏ−ブロモフエノキシ）
シクロペンテン
アルゴン雰囲気下、水素化ナトリウム（50％鉱
油デイスパージヨン）2.78ｇをｎ−ヘキサン（10
ml×２）にて洗浄し、１，２−ジメトキシエタン
20mlに懸濁させ、氷冷下で攪拌している中へｏ−
ブロモフエノール6.67mlを滴下した。この溶液を
−30゜に冷却し、１，２−ジメトキシエタン25ml
に溶解した３，５−シス−ジブロモシクロペンテ
ン6.24ｇを加え、室温で１日攪拌した。析出した
結晶を過し、液を濃縮して得られた結晶を合
わせて水、エーテル、石油エーテルで洗浄後、減
圧下乾燥し、ほぼ純品が6.0ｇ得られた。 IR: Infrared absorption spectrum (only major bands listed) NMR: Proton nuclear magnetic resonance spectrum Mass: Mass spectrum Example 1 3,5-cis-bis(o-bromophenoxy)
Cyclopentene Under an argon atmosphere, 2.78 g of sodium hydride (50% mineral oil dispersion) was added to n-hexane (10%
ml x 2) and 1,2-dimethoxyethane.
Suspend in 20 ml and add o-
6.67 ml of bromophenol was added dropwise. Cool this solution to -30° and add 25 ml of 1,2-dimethoxyethane.
6.24 g of 3,5-cis-dibromocyclopentene dissolved in was added, and the mixture was stirred at room temperature for one day. The precipitated crystals were filtered, the liquid was concentrated, and the resulting crystals were combined, washed with water, ether, and petroleum ether, and then dried under reduced pressure to obtain 6.0 g of an almost pure product.
m.p.：138.0〜138.5゜
IR（KBr）νcm-1：1585、1570、1165、992、
790
NMR（CDCl3）δ：2.21（1H，dd，Ｊ＝14.0O
Hz，5.0Hz）、3.08（1H，dd，Ｊ＝14.0Hz、7.0
Hz）、5.20（1H，dd，Ｊ＝7.0Hz、5.0Hz）、
6.30（2H，Ｓ）、6.80〜7.50（8H，ｍ）
C7H15O2Br2としての計算値：
Ｃ；49.66、Ｈ；3.68
C7H15O2Br2としての実測値：
Ｃ；49.76、Ｈ；3.56
実施例 ２
３，５−シス−ビス（ｏ−ブロモフエノキシ）
シクロペンテン
メタノール6.1にKOH（85％）610.5ｇ
（9.248mol）を溶かし、氷冷した後、ｏ−ブロモ
フエノール1600、１ｇ（9.248mol）をメタノー
ル１に溶かしたものを１時間かけて加えた。溶
媒を留去した後、THF800mlで共沸脱水し、真空
ポンプで乾燥した。 mp: 138.0~138.5゜ IR (KBr) νcm -1 : 1585, 1570, 1165, 992,
790 NMR (CDCl 3 ) δ: 2.21 (1H, dd, J = 14.0O
Hz, 5.0Hz), 3.08 (1H, dd, J=14.0Hz, 7.0
Hz), 5.20 (1H, dd, J=7.0Hz, 5.0Hz),
6.30 (2H, S), 6.80-7.50 ( 8H , m) Calculated value as C7H15O2Br2 : C; 49.66, H; 3.68 Actual value as C7H15O2Br2 : C ; 49.76, H; 3.56 Example 2 3,5-cis-bis(o-bromophenoxy)
Cyclopentene Methanol 6.1 to KOH (85%) 610.5g
(9.248 mol) was dissolved and cooled on ice, and then a solution of 1 g (9.248 mol) of o-bromophenol 1600 dissolved in 1 methanol was added over 1 hour. After distilling off the solvent, the residue was azeotropically dehydrated with 800 ml of THF and dried using a vacuum pump.
ｏ−ブロモフエノールのカリウム塩の収量：
2067.0ｇ
収率：105.9％
上述のｏ−ブロモフエノールのカリウム塩を
THF2.6に溶かし、ｎ−Bu4NBr14.90ｇ
（46.2mmol）を加えて氷冷した。次に、３，５−
シス−ジブロモシクロペンテン1096.9ｇ
（4.855mol）をTHF1.1に溶かして冷却したも
のを一度に加えた。そして、氷冷したまま１晩攪
拌した。反応液に水1.2を加えて攪拌し、溶媒
を留去した後、析出した結晶を1NNaOHaq5、
水５で２回、メタノール３、シクロヘキサン
２で洗浄した後、ｎ−ヘキサン500mlで２回か
け洗いした。得られた結晶を１晩真空ポンプで乾
燥すると、標題化合物1352.0ｇが得られた。な
お、本実施例で得られた化合物は、実施例１と同
じ物性を有していた。 Yield of potassium salt of o-bromophenol:
2067.0g Yield: 105.9% The above potassium salt of o-bromophenol was
Dissolved in THF2.6, n-Bu 4 NBr14.90g
(46.2 mmol) was added and cooled on ice. Next, 3,5-
Cis-dibromocyclopentene 1096.9g
(4.855 mol) was dissolved in THF1.1 and cooled and added all at once. Then, the mixture was stirred overnight while cooling on ice. After adding 1.2 parts of water to the reaction solution and stirring, and distilling off the solvent, the precipitated crystals were mixed with 1N NaOHaq5,
After washing with 5 portions of water twice, 3 portions of methanol, and 2 portions of cyclohexane, it was washed twice with 500 ml of n-hexane. The obtained crystals were dried overnight using a vacuum pump to obtain 1352.0 g of the title compound. Note that the compound obtained in this example had the same physical properties as in Example 1.
収率：71.3％
実施例 ３
3a，8b−シス−ジヒドロ−3H−シクロペンタ
［ｂ］ベンゾフラン
３，５−シス−ビス（ｏ−ブロモフエノキシ）
シクロペンテン6.0ｇをテトラヒドロフラン５ml
に溶かし、−78℃に冷却し、ｎ−ブチルリチウム
のｎ−ヘキサン溶液（2.0M）0.72ml加え、10分
後−10℃に上げ、約３時間攪拌した。反応混合物
に塩化アンモニウの飽和水溶液を加え、エーテル
で３回抽出し、有機層を合わせて乾燥後濃縮する
と５ｇの油状物質が得られた。この油状物質を蒸
留し、純粋な標題化合物1.84ｇが得られた。 Yield: 71.3% Example 3 3a,8b-cis-dihydro-3H-cyclopenta[b]benzofuran 3,5-cis-bis(o-bromophenoxy)
6.0g of cyclopentene and 5ml of tetrahydrofuran
The solution was cooled to -78°C, 0.72ml of n-butyllithium in n-hexane solution (2.0M) was added, and after 10 minutes the temperature was raised to -10°C and stirred for about 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, extracted three times with ether, and the organic layers were combined, dried, and concentrated to obtain 5 g of an oily substance. Distillation of this oil gave 1.84 g of pure title compound.
b.p.：77.8〜78.8℃／0.1mmHg
収 率：40％
IR（液膜法）νcm-1：3060、1602、1582
NMR（CDCl3）δ：2.80（1H，dd，Ｊ＝2.2，
0.5Hz）、2.82（1H，dd，Ｊ＝5.2，0.5Hz）、
4.35（1H，ｄ，Ｊ＝7.8Hz）、5.43（1H，ddd，
Ｊ＝7.8Hz，5.2，2.2Hz）、5.71（2H，ｓ）、
6.95（4H，ｍ）
Mass：158（M+）
［発明の効果］
本発明は上述したように、3a，8b−シス−ジ
ヒドロ−3H−シクロペンタ［ｂ］ベンゾフラン
を二重結合の異性体を混入することなく、選択的
に製造しうるものである。また、高価な触媒も不
要であり、工業的製法として非常に有用である。 bp: 77.8-78.8℃/0.1mmHg Yield: 40% IR (liquid film method) νcm -1 : 3060, 1602, 1582 NMR (CDCl 3 ) δ: 2.80 (1H, dd, J = 2.2,
0.5Hz), 2.82 (1H, dd, J=5.2, 0.5Hz),
4.35 (1H, d, J = 7.8Hz), 5.43 (1H, ddd,
J=7.8Hz, 5.2, 2.2Hz), 5.71 (2H, s),
6.95 (4H, m) Mass: 158 (M + ) [Effects of the invention] As described above, the present invention provides 3a,8b-cis-dihydro-3H-cyclopenta[b]benzofuran mixed with a double bond isomer. It can be manufactured selectively without having to do so. Furthermore, it does not require an expensive catalyst and is very useful as an industrial production method.
Claims (1)
ペンテンと反応させ、式（） で示される化合物とし、 次いで、有機リチウム試薬と反応させることを
特徴とする式（） で示されるシクロペンタ［ｂ］ベンゾフランの製
造方法。[Claims] 1. The following general formula () (M represents Na or K) is reacted with 3,5-cis dibromocyclopentene to form the formula () A compound represented by the formula (), which is then reacted with an organolithium reagent. A method for producing cyclopenta[b]benzofuran shown by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7222589A JPH01279878A (en) | 1989-03-24 | 1989-03-24 | Production of cyclopenta(b)benzofuran |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7222589A JPH01279878A (en) | 1989-03-24 | 1989-03-24 | Production of cyclopenta(b)benzofuran |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2953781A Division JPS57144277A (en) | 1981-03-02 | 1981-03-02 | Cyclopentabenzofuran derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01279878A JPH01279878A (en) | 1989-11-10 |
| JPH0369908B2 true JPH0369908B2 (en) | 1991-11-05 |
Family
ID=13483106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7222589A Granted JPH01279878A (en) | 1989-03-24 | 1989-03-24 | Production of cyclopenta(b)benzofuran |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01279878A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0915073B1 (en) * | 1997-02-21 | 2003-08-13 | Toray Industries, Inc. | Process for producing optically active isomers of tricyclic compounds |
-
1989
- 1989-03-24 JP JP7222589A patent/JPH01279878A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01279878A (en) | 1989-11-10 |
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