JPH03153680A - Biphenyl compound and its preparation - Google Patents
Biphenyl compound and its preparationInfo
- Publication number
- JPH03153680A JPH03153680A JP1290942A JP29094289A JPH03153680A JP H03153680 A JPH03153680 A JP H03153680A JP 1290942 A JP1290942 A JP 1290942A JP 29094289 A JP29094289 A JP 29094289A JP H03153680 A JPH03153680 A JP H03153680A
- Authority
- JP
- Japan
- Prior art keywords
- dimethoxybiphenyl
- bis
- methylenedioxy
- hydroxymethyl
- methylating agent
- 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
- -1 Biphenyl compound Chemical class 0.000 title description 4
- 235000010290 biphenyl Nutrition 0.000 title 1
- 239000004305 biphenyl Substances 0.000 title 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title 1
- 239000012022 methylating agents Substances 0.000 claims abstract description 8
- UIMPAOAAAYDUKQ-UHFFFAOYSA-N 1-methoxy-4-(4-methoxyphenyl)benzene Chemical group C1=CC(OC)=CC=C1C1=CC=C(OC)C=C1 UIMPAOAAAYDUKQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims description 11
- KXMTXZACPVCDMH-UHFFFAOYSA-N methyl 4-[5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate Chemical group COC(=O)C1=CC(OC)=C2OCOC2=C1C1=C2OCOC2=C(OC)C=C1CO KXMTXZACPVCDMH-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract description 3
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 208000019423 liver disease Diseases 0.000 abstract description 2
- 238000010992 reflux Methods 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- AVAYCNNAMOJZHO-UHFFFAOYSA-N [Na+].[Na+].[O-]B[O-] Chemical compound [Na+].[Na+].[O-]B[O-] AVAYCNNAMOJZHO-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、肝疾患治療剤として有用な６−メトキシカル
ボニル−６゛−ヒドロキシメチル−２。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention provides 6-methoxycarbonyl-6'-hydroxymethyl-2 useful as a therapeutic agent for liver diseases.
３、２’．３’−ビス（メチレンジオキシ）−４．４′
ジメトキシビフエニルの製造方法およびその製造中間体
に関する。3, 2'. 3'-bis(methylenedioxy)-4.4'
This invention relates to a method for producing dimethoxybiphenyl and an intermediate for its production.
従来の技術
６−メトキシカルボニル−６゛−ヒドロキシメチル−２
．３．２’，３’−ビス（メチレンジオキシ）−４．４
’−ジメトキシビフェニルの製造方法としては、１ 、
２ 、１０．１１−ビス（メチレンジオキシ）−５、
７−シヒドロー３，９−ジメトキシ−５−オキソジベン
ゾ［ｃ，ｅコオキセビンをメタノールと反応させる方法
が知られている（特開昭６３−１９２７７１号公報）。Prior art 6-methoxycarbonyl-6'-hydroxymethyl-2
．． 3.2',3'-bis(methylenedioxy)-4.4
The method for producing '-dimethoxybiphenyl includes 1,
2, 10.11-bis(methylenedioxy)-5,
A method of reacting 7-sihydro-3,9-dimethoxy-5-oxodibenzo[c,e-coxebine with methanol is known (Japanese Unexamined Patent Publication No. 192771/1983).
しかしながら、上記の方法は、反応が平衡反応であるた
め長時間の還流にも拘らず反応が完結せず、収率が低く
、実用的に十分ではない。However, in the above method, since the reaction is an equilibrium reaction, the reaction is not completed despite refluxing for a long time, resulting in a low yield and is not sufficient for practical use.
明が解決しようとする課題
本発明は６−メドキシカルポニルー６′−ヒドロキシメ
チル−２，３，２’、３’−ビス（メチレンジオキシ＞
−４，４’−ジメトキシビフェニルを製造するに当り、
収率の良い、実用的な製造方法およびその製造中間体を
提供することを目的とする。Problems to be Solved by the present invention The present invention relates to 6-medoxycarponyl-6'-hydroxymethyl-2,3,2',3'-bis(methylenedioxy>
In producing -4,4'-dimethoxybiphenyl,
The purpose of the present invention is to provide a practical manufacturing method with good yield and intermediates for the manufacturing process.
課 を解決するための手段
本発明者らは、従来法に代わる別途製造法を種々検討し
た結果、６−カルポキシー６゛−ヒドロキシメチル−２
，３，２’、３’−ビス（メチレンジオキシ）−４，４
’−ジメトキシビフェニルをメチル化剤と反応させるこ
とにより、上記課題を解決できることを見出し本発明を
完成した。Means for Solving Problems As a result of various studies on alternative production methods to replace conventional methods, the present inventors found that 6-carpoxy 6′-hydroxymethyl-2
,3,2',3'-bis(methylenedioxy)-4,4
The present invention has been completed by discovering that the above problems can be solved by reacting '-dimethoxybiphenyl with a methylating agent.
以下、本発明を説明する。The present invention will be explained below.
本発明は、６−メトキシカルボニル−６゛−ヒドロキシ
メチル−２，３，２’、３’−ビス（メチレンジオキシ
）−４，４’−ジメトキシビフェニルを製造するに当り
、６−カルポキシー６′−ヒドロキシメチル−２，３，
２’、３’−ビス（メチレンジオキシ）−４，４’−ジ
メトキシビフェニルをメチル化剤と反応させることを特
徴とする６−ノドキシカルボニル−６′〜ヒドロキシメ
チル−２，３，２’３゛−ビス（メチレンジオキシ）−
４，４’−ジメトキシビフェニルの製造方法である。The present invention relates to the production of 6-methoxycarbonyl-6'-hydroxymethyl-2,3,2',3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl. -Hydroxymethyl-2,3,
6-nodoxycarbonyl-6'-hydroxymethyl-2,3,2' characterized by reacting 2',3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl with a methylating agent. 3゛-bis(methylenedioxy)-
This is a method for producing 4,4'-dimethoxybiphenyl.
また、他の本発明は、６−カルボキシ−６゛ヒドロキシ
メチル−２，３，２’、３’−ビスくメチレンジオキシ
）−４，４’−ジメトキシビフェニルである。Another aspect of the present invention is 6-carboxy-6'hydroxymethyl-2,3,2',3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl.
本発明において、メチル化剤とは、ジメチル硫酸、ヨウ
化メチル、臭化メチル、パラトルエンスルホン酸メチル
、メタンスルホン酸メチル、ジアゾメタンなどである。In the present invention, the methylating agent includes dimethyl sulfate, methyl iodide, methyl bromide, methyl paratoluenesulfonate, methyl methanesulfonate, diazomethane, and the like.
メチル化剤の使用量は原料に対して１〜５モル当量が望
ましい。ジアゾメタン以外の上記メチル化剤を使用する
場合は、塩基の存在下に反応を実施することにより好ま
しい結果を得ることができる。ここで塩基とは、次酸力
ノウム、炭酸ナトリウム、炭酸水素ナトリウムなどの無
機塩基及びピリジン、トリエチルアミンなどの有機塩基
が挙げられる。塩基の使用量は、メチル化剤と同様に１
〜５モル当量が望ましい。反応溶媒はアセトン、テトラ
ヒドロフラン、ジエチルエーテル、クロロホルム、ジク
ロロメタン、酢酸エチル、ジオキサン、Ｎ、Ｎ−ジメチ
ルホルムアミド、ジメチルスルホキシドなどを用いるこ
とかでさる。反応温度は、−１０″Ｃかも使用する溶媒
の沸点温度の間から適宜決定すれば良い。The amount of the methylating agent used is preferably 1 to 5 molar equivalents based on the raw material. When using the above-mentioned methylating agents other than diazomethane, preferred results can be obtained by carrying out the reaction in the presence of a base. Here, the base includes inorganic bases such as subacid, sodium carbonate, and sodium bicarbonate, and organic bases such as pyridine and triethylamine. The amount of base used is 1
~5 molar equivalents are desirable. As the reaction solvent, acetone, tetrahydrofuran, diethyl ether, chloroform, dichloromethane, ethyl acetate, dioxane, N,N-dimethylformamide, dimethyl sulfoxide, etc. can be used. The reaction temperature may be appropriately determined between -10''C and the boiling point temperature of the solvent used.
反応の終了は、シリカゲル薄層クロマトグラフィーによ
り原料の消失を見て決定される。The completion of the reaction is determined by observing the disappearance of starting materials by silica gel thin layer chromatography.
発明の効果
本発明の方法により、従来法に比し高収率、高純度で６
−メトキシカルボニル−６″−ヒドロキシメチル−２，
３，２’、３’−ビス（メチレンジオキシ）−４，４’
−ジメトキシビフェニルを製造することが可能となった
。また、その製造のための重要な中間体が提供きれた。Effects of the Invention The method of the present invention allows the production of
-methoxycarbonyl-6″-hydroxymethyl-2,
3,2',3'-bis(methylenedioxy)-4,4'
-It became possible to produce dimethoxybiphenyl. In addition, an important intermediate for its production has been provided.
火蓋」 次に、実施例により本発明をより具体的に説明する。"Fire cover" Next, the present invention will be explained in more detail with reference to Examples.
実施例１
５．６．５’、６’−ビス（メチレンジオキシ）−４゜
４゛−ジメトキシビフェニル−２，２゛−ジカルボン酸
無水物（特開昭６３−１９２７７１号公報）８６ｇを水
素化ホウ素ナトリウム２１．５ｇを含むＮ、Ｎ−ジメチ
ルホルムアミド（４３０ｍＱ ）溶液に０〜１５°Ｃで
攪拌下徐々に加え、０〜１５°Ｃで１．５時間反応を行
った。Example 1 86 g of 5.6.5',6'-bis(methylenedioxy)-4゜4゛-dimethoxybiphenyl-2,2゛-dicarboxylic acid anhydride (Japanese Patent Application Laid-open No. 192771/1983) was heated with hydrogen. The mixture was gradually added to a solution of N,N-dimethylformamide (430 mQ) containing 21.5 g of sodium boronate with stirring at 0 to 15°C, and the reaction was carried out at 0 to 15°C for 1.5 hours.
反応終了後、冷水８６０ｍ１を０〜１５°Ｃで反応液に
滴下し、次にジクロロメタン１８０ｍＱ添加後、塩酸で
酸性とし、析出した結晶を濾別した。得られた結晶を無
水炭酸ナトリウム２４．５ｇを含む水溶液（水４９０Ｔ
＋１１１ ）に溶解し、ジクロロメタン９０ｍＱで２回
洗浄後、ジクロロメタン１８０ｍＱを加え、濃塩酸５０
ｍＱで酸性となし、析出した結晶を濾過、水洗、乾燥し
て６−カルポキシー６゛−ヒドロキシメチル−２゜３．
２’、３’−ビス（メチレンジオキシ）−４，４゜ジメ
トキシビフェニル８０．９ｇを得た。After the reaction was completed, 860 ml of cold water was added dropwise to the reaction solution at 0 to 15°C, and then 180 mQ of dichloromethane was added, acidified with hydrochloric acid, and the precipitated crystals were filtered off. The obtained crystals were dissolved in an aqueous solution containing 24.5 g of anhydrous sodium carbonate (490T water).
After washing twice with 90 mQ of dichloromethane, 180 mQ of dichloromethane was added, and 50 mQ of concentrated hydrochloric acid was added.
It was made acidic with mQ, and the precipitated crystals were filtered, washed with water, and dried to give 6-carpoxy-6'-hydroxymethyl-2'3.
80.9 g of 2',3'-bis(methylenedioxy)-4,4°dimethoxybiphenyl was obtained.
ｍ、ｐ、 １９２〜１９５℃
実施例２
１ 、２．１０．１１−ビス（メチレンジオキシ）−５
，７−シヒドロー３，９−ジメトキシ−５−オキソジベ
ンゾ［ｃ、ｅコオキセビン（特開昭６３−１９２７７１
号公報）５０ｇを水５００ｔｄに懸濁し、次に水酸化力
ノウム１５．６ ｇを加え、４．５時間還流した。反応
液を冷却後、塩酸酸性となし、析出した結晶を濾取し、
水洗、乾燥して６−カルポキシー６′−ヒドロキシメチ
ル−２，３，２’、３’−ビス（メチレンジオキシ）−
４，４’−ジメトキシビフェニル４７．８ ｇを得た。m, p, 192-195°C Example 2 1 , 2.10.11-bis(methylenedioxy)-5
,7-sihydro-3,9-dimethoxy-5-oxodibenzo[c,e cooxebine (JP-A-63-192771
50 g of the suspension was suspended in 500 td of water, then 15.6 g of hydroxide was added and refluxed for 4.5 hours. After cooling the reaction solution, it was made acidic with hydrochloric acid, and the precipitated crystals were collected by filtration.
Washed with water and dried to form 6-carpoxy 6'-hydroxymethyl-2,3,2',3'-bis(methylenedioxy)-
47.8 g of 4,4'-dimethoxybiphenyl was obtained.
実施例３
６−カルポキシー６゛−ヒドロキシメチル−２゜３．２
’、３’−ビス（メゾレンジオキシ）−４，４ジメトキ
シビフェニル８０．９ ｇをアセトン１３０９ｍ１＋に
加熱（４０〜４５°Ｃ）溶解し、無水炭酸カリウム４０
．４５ｇを加え、４０〜４５℃で１５分間攪拌した。次
に、ジメチル硫酸２２．２５ｍＱを加え、４０〜４５°
Ｃで２，５時間攪拌した。反応終了後、不溶物を濾過し
、濾液に１０％アンモニア水４０ｍ１ｌを加え、室温で
１時間放置した。その後、アセトンを３０℃で減圧留去
し、得られた残渣を酢酸エチル４００ｍ１に溶解し、有
機層を１０５食塩水５０ｍＱで３回洗浄後、無水硫酸ナ
トリウムで乾燥した。硫酸ナトリウムを濾去し、酢酸エ
チルの約２／３を３０〜４０°Ｃで減圧留去し、水冷下
、２時間攪拌した。析出した白色粉末結晶を濾過し、酢
酸エチル５０ｙｎＱで洗浄後、乾燥して６−メトキシカ
ルボニル−６゛−ヒドロキシメチル−２゜３．２’、３
’−ビス（メチレンジオキシ）−４，４’ジメトキシビ
フエニル６７ｇを得た。Example 3 6-carpoxy 6゛-hydroxymethyl-2゜3.2
80.9 g of ',3'-bis(mesoledioxy)-4,4 dimethoxybiphenyl was dissolved in 1309 ml of acetone by heating (40 to 45°C), and 40 g of anhydrous potassium carbonate was dissolved in 1309 ml of acetone.
．． 45 g was added and stirred at 40-45°C for 15 minutes. Next, add 22.25 mQ of dimethyl sulfate and
The mixture was stirred at C for 2.5 hours. After the reaction was completed, insoluble matter was filtered, and 40 ml of 10% aqueous ammonia was added to the filtrate, which was left at room temperature for 1 hour. Thereafter, acetone was distilled off under reduced pressure at 30° C., the resulting residue was dissolved in 400 ml of ethyl acetate, the organic layer was washed three times with 50 mQ of 105 brine, and then dried over anhydrous sodium sulfate. Sodium sulfate was filtered off, about 2/3 of the ethyl acetate was distilled off under reduced pressure at 30 to 40°C, and the mixture was stirred for 2 hours under water cooling. The precipitated white powder crystals were filtered, washed with 50ynQ of ethyl acetate, and dried to give 6-methoxycarbonyl-6゛-hydroxymethyl-2゜3.2',3
67 g of '-bis(methylenedioxy)-4,4'dimethoxybiphenyl was obtained.
ｍ、ｐ、 １３７〜１４０℃
実施例４
６−カルポキシー６゛−ヒドロキシメチル−２゜３．２
’、３’−ビス（メチレンジオキシ）−４，４’ジメト
キシビフェニル３．７６ ｇをアセトン３７．６ｍ１ｌ
に加熱（４０〜４５℃）溶解し、無水炭酸カリウム３．
７６ ｇを加え、４０〜４５℃で１５分間攪拌した０次
に、室温まで冷却し、ヨウ化メチル１．２５ｍを加え、
同温度で２４時間攪拌した。反応終了後、不溶物を濾過
し、濾液を減圧留去し、得られた残渣を酢酸エチル３０
ＩＴＩＱに溶解し、有機層を１０２食塩水５ｍｌで３回
洗浄後、無水硫酸ナトリウムで乾燥した。硫酸ナトリウ
ムを濾去し、酢酸エチルの約２／３を３０〜４０゛Ｃで
減圧留去し、水冷下、２時間攪拌した。析出した白色粉
末結晶を濾過し、酢酸エチル５ｍｌで洗浄後、乾燥して
、６−メドキシカルポニルー６゛−ヒドロキシメチル−
２，３，２’、３’−ビス（メチレンジオキシ）−４，
４’−ジメトキシビフェニル３、０６ ｇを得た。m, p, 137-140°C Example 4 6-carpoxy 6゛-hydroxymethyl-2゜3.2
3.76 g of ',3'-bis(methylenedioxy)-4,4'dimethoxybiphenyl was added to 37.6 ml of acetone.
3. Heat (40-45°C) to dissolve anhydrous potassium carbonate.
76 g was added and stirred for 15 minutes at 40-45°C. Next, it was cooled to room temperature, and 1.25 m of methyl iodide was added.
The mixture was stirred at the same temperature for 24 hours. After the reaction was completed, insoluble materials were filtered, the filtrate was distilled off under reduced pressure, and the resulting residue was diluted with ethyl acetate (30%).
It was dissolved in ITIQ, and the organic layer was washed three times with 5 ml of 102 brine, and then dried over anhydrous sodium sulfate. Sodium sulfate was filtered off, about 2/3 of the ethyl acetate was distilled off under reduced pressure at 30-40°C, and the mixture was stirred for 2 hours under water cooling. The precipitated white powder crystals were filtered, washed with 5 ml of ethyl acetate, and dried to give 6-medoxycarbonyl-6'-hydroxymethyl-
2,3,2',3'-bis(methylenedioxy)-4,
3.06 g of 4'-dimethoxybiphenyl was obtained.
実施例５
実施例４において、ヨウ化メチルの代わりに、パラトル
エンスルホン酸メチル２．２３ｇＬ用いて、実施例４と
同様に反応、後処理して、６−メトキシカルボニル−６
゛−ヒドロキシメチル−２，３゜２’、３’−ビス（メ
チレンジオキシ）−４，４’−ジメトキシビフェニル２
．６５ ｇを得た。Example 5 In Example 4, 2.23 gL of methyl p-toluenesulfonate was used instead of methyl iodide, and the reaction and post-treatment were carried out in the same manner as in Example 4 to produce 6-methoxycarbonyl-6.
゛-Hydroxymethyl-2,3゜2',3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl 2
．． 65 g was obtained.
Claims (2)
ル−２，３，２′，３′−ビス（メチレンジオキシ）−
４，４′−ジメトキシビフェニルを製造するに当り、６
−カルボキシ−６′−ヒドロキシメチル−２，３，２′
，３′−ビス（メチレンジオキシ）−４，４′−ジメト
キシビフェニルをメチル化剤と反応させることを特徴と
する６−メトキシカルボニル−６′−ヒドロキシメチル
−２，３，２′，３′−ビス（メチレンジオキシ）−４
，４′−ジメトキシビフェニルの製造方法(1) 6-methoxycarbonyl-6'-hydroxymethyl-2,3,2',3'-bis(methylenedioxy)-
In producing 4,4'-dimethoxybiphenyl, 6
-carboxy-6'-hydroxymethyl-2,3,2'
, 3'-bis(methylenedioxy)-4,4'-dimethoxybiphenyl is reacted with a methylating agent. 6-methoxycarbonyl-6'-hydroxymethyl-2,3,2',3' -bis(methylenedioxy)-4
, 4'-dimethoxybiphenyl manufacturing method
３，２′，３′−ビス（メチレンジオキシ）−４，４′
−ジメトキシビフェニル(2) 6-carboxy-6'-hydroxymethyl-2,
3,2',3'-bis(methylenedioxy)-4,4'
-dimethoxybiphenyl
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1290942A JPH03153680A (en) | 1989-11-08 | 1989-11-08 | Biphenyl compound and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1290942A JPH03153680A (en) | 1989-11-08 | 1989-11-08 | Biphenyl compound and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03153680A true JPH03153680A (en) | 1991-07-01 |
Family
ID=17762488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1290942A Pending JPH03153680A (en) | 1989-11-08 | 1989-11-08 | Biphenyl compound and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03153680A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101550127A (en) * | 2008-03-31 | 2009-10-07 | 中国医学科学院药物研究所 | Two crystal substances of bicycle-ethanol, preparation method, pharmaceutical composition and application thereof |
| CN102617544A (en) * | 2012-03-13 | 2012-08-01 | 南京工业大学 | Novel method for preparing bicyclol |
| CN103242286A (en) * | 2013-01-24 | 2013-08-14 | 辽宁亿灵科创生物医药科技有限公司 | Bicyclol medical composition and preparation method thereof |
| CN107141278A (en) * | 2017-06-06 | 2017-09-08 | 北京元延医药科技股份有限公司 | The method that bicyclic alcohols are prepared using DDB |
| CN111205263A (en) * | 2020-04-22 | 2020-05-29 | 北京鑫开元医药科技有限公司 | Preparation method and application of bicyclol |
-
1989
- 1989-11-08 JP JP1290942A patent/JPH03153680A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101550127A (en) * | 2008-03-31 | 2009-10-07 | 中国医学科学院药物研究所 | Two crystal substances of bicycle-ethanol, preparation method, pharmaceutical composition and application thereof |
| CN102617544A (en) * | 2012-03-13 | 2012-08-01 | 南京工业大学 | Novel method for preparing bicyclol |
| CN103242286A (en) * | 2013-01-24 | 2013-08-14 | 辽宁亿灵科创生物医药科技有限公司 | Bicyclol medical composition and preparation method thereof |
| CN107141278A (en) * | 2017-06-06 | 2017-09-08 | 北京元延医药科技股份有限公司 | The method that bicyclic alcohols are prepared using DDB |
| CN111205263A (en) * | 2020-04-22 | 2020-05-29 | 北京鑫开元医药科技有限公司 | Preparation method and application of bicyclol |
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