JPS62195343A - Novel manufacture of compound - Google Patents
Novel manufacture of compoundInfo
- Publication number
- JPS62195343A JPS62195343A JP3229487A JP3229487A JPS62195343A JP S62195343 A JPS62195343 A JP S62195343A JP 3229487 A JP3229487 A JP 3229487A JP 3229487 A JP3229487 A JP 3229487A JP S62195343 A JPS62195343 A JP S62195343A
- Authority
- JP
- Japan
- Prior art keywords
- methyllithium
- metal derivative
- naphthyl
- methoxy
- methyl metal
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 229910003002 lithium salt Inorganic materials 0.000 claims description 4
- 159000000002 lithium salts Chemical class 0.000 claims description 4
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- -1 methoxy-2-naphthyl Chemical group 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 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 claims description 2
- 239000003960 organic solvent Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960004270 nabumetone Drugs 0.000 description 2
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- LWOTXBQKJLOAOZ-UHFFFAOYSA-N 1-(6-methoxynaphthalen-2-yl)propan-1-one Chemical compound C1=C(OC)C=CC2=CC(C(=O)CC)=CC=C21 LWOTXBQKJLOAOZ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/004—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with organometalhalides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
〔発明の目的〕
本発明は４−（６−メドキシー２−ナフテルンブタンー
２−オンの製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION OBJECTS OF THE INVENTION The present invention relates to a process for producing 4-(6-medoxy-2-naphternebutan-2-one).
米国特許第４０６１７７９号明細４！は４−（６−メド
キシー２−ナフチル］ブタンー２−オン〔ナブメトン（
ｎａｂｕｍｅｌｏｎｅＪ）及びそれのリューマチ及び関
節炎症状の治療における用途を記載している。多数のこ
の化合物の製造方法も記載されている。米国特許第４２
２１７４１号及び同第４２４７７０９号明細書はナブメ
トンの別の製造方法を記載している。US Patent No. 4,061,779 Specification 4! is 4-(6-medoxy-2-naphthyl)butan-2-one [nabumetone (
nabumelone J) and its use in the treatment of rheumatoid and arthritic conditions. A number of methods for making this compound have also been described. US Patent No. 42
No. 21741 and No. 4247709 describe another method for producing nabumetone.
本発明において、ナプメトンの別の製造方法が見出され
、この方法はカルゼン酸をメチル金属誘導体と反応させ
ることを特徴とする。In the present invention, another method for the production of napmetone has been found, which is characterized in that calzenic acid is reacted with a methyl metal derivative.
従って、本発明は式（１）
で表わされる化合物ま危はそのアルカリ金属塩をメチル
金属誘導体と反応させることを含む４−（６−メドキシ
ー２−ナフチルノブタン−２−オンの製造方法全提供す
る。Therefore, the present invention provides a complete method for producing 4-(6-medoxy-2-naphthylnobutan-2-one), which comprises reacting a compound represented by formula (1) or an alkali metal salt thereof with a methyl metal derivative. do.
式（１）で表わされる化合物は有利には酸の金属塩、好
ましくはリチウム塩である。The compound of formula (1) is advantageously a metal salt of an acid, preferably a lithium salt.
好適なメチル金属誘導体にはＯＨ５Ｗｉｔ Ｈａｔ（式
中、ＨａｔはヨードのようなハロゲンであるＩまたはメ
チルリチウムが含まれる。好ましくは、メチル金属誘導
体はメチルリチウムである。Suitable methyl metal derivatives include OH5Wit Hat, where Hat is a halogen such as iodine, or methyllithium. Preferably, the methyl metal derivative is methyllithium.
反応は乾燥ジエチルエーテルまたはテトラヒドロフラン
のような不活性醇媒、好ましくはテトラヒドロフラン中
で、メチル金属誘導体がＯＨ３’１４ｆＨａＬであると
きは還流温度でまたはメチルリチウムが使用されるとき
は０〜５０℃で起きる。The reaction takes place in an inert medium such as dry diethyl ether or tetrahydrofuran, preferably tetrahydrofuran, at reflux temperature when the methyl metal derivative is OH3'14fHaL or from 0 to 50°C when methyllithium is used. .
式（１）で表わされる化合ｖＪは公知化合物である。Compound vJ represented by formula (1) is a known compound.
以下、実施例により本発明を例示する。The invention will now be illustrated by examples.
実施例
１．７リーデル・クラ７ツ（Ｆｒ１ｅｄｅｌ −０ｒａ
ｆｔａＪ反応
Ａｔ２０ｔ２ （４０，５ｙ Ｊを冷却攪拌下のニトロ
エタン（２２５３ｍＪに＋２℃にて少量ずつ添加し、次
いで２−メトキシナフタレン（４５ｆ）を１０分間要し
て添加した。温度は一５℃に下がり、赤色／褐色混合物
は１０分間要して添加した塩化プロピオニル（２８，２
ｄｌで処理した。混合物を＋加湿した。水（２５０ｄｌ
を１５分分間上て添加し、有機生成物をｖｉＤＣで抽出
し、溶媒を蒸発させることによシ粗生成物（４６ｔｌを
得た。生成物をセライ）（１０，１の存在下にて温へブ
タン（＋８５℃矛に醇解し、熱濾過し、放冷することに
より薄黄色固体（２８９，収率４５チＪを得た。Example 1.7 Friedel-0ra
ftaJ reaction At20t2 (40,5y J was added portionwise to nitroethane (2253 mJ) under cooling stirring at +2°C, then 2-methoxynaphthalene (45f) was added over 10 minutes. The temperature was lowered to -5°C. , the red/brown mixture was mixed with propionyl chloride (28,2
treated with dl. The mixture was +humidified. Water (250dl
was added for 15 minutes, the organic product was extracted with viDC and the crude product (46 tl was obtained by evaporating the solvent. The product was heated in the presence of Cely) (10,1). Hebutane (dissolved at +85°C, filtered hot, and allowed to cool gave a pale yellow solid (289, yield: 45 cm).
２−メトキシ−６−プロピオニルナフタレン（２１，４
ｙ ＋、硫黄（４，８ｙ Ｉ及びモルホリン（１３ａｄ
ｌを１２５℃で１６時間加熱した。次いで、メタノー
ル＋５０ｍ／Ｊ中の水酸化ナトリウム（ｔ Ｏ，Ｓ ｆ
Ｊを添加し、混合物を更に６時間還流加熱し、ｐＨが
２になるまでＨＯ／！、／水中に注加した。2-methoxy-6-propionylnaphthalene (21,4
y +, sulfur (4,8y I and morpholine (13ad
1 was heated at 125° C. for 16 hours. Then sodium hydroxide (t O, S f
J was added and the mixture was heated at reflux for a further 6 hours until the pH was 2 HO/! ,/poured into water.
有機生成物を抽出した。順相ＬＯ（ヘキサン＝ＩＰん：
ＴｄＤＯ９２：４：４）は生成物がｔＢ４．０１分及び
ｔ Ｂ ４．２５分の２塊の主成分を含有していること
を示した（尚、純粋な３− （６’−メトキシ−２′−
ナフチルｌプロピオン酸はｔ Ｂ ４．２０分であるＪ
。Organic products were extracted. Normal phase LO (hexane=IP):
TdDO92:4:4) showed that the product contained two main components with tB 4.01 min and tB 4.25 min (note that pure 3-(6'-methoxy-2 ′−
Naphthyl l propionic acid has t B 4.20 min J
.
生成物の融点は１４３℃であつ次（尚、目的の酸の場合
は１５４℃）。The melting point of the product is 143°C (154°C for the target acid).
３− （６’−メトキシ−２′〜ナフチル」プロピオｙ
ｚｏリチウム塩（５，Ｏｙ ＪのｒＨＦ （ｔ ５０
ｍ Ｊ中懸濁液を攪拌下で約−ｔｏｔ’まで冷却した。3-(6'-methoxy-2'-naphthyl) propioy
zo lithium salt (5, Oy J rHF (t 50
The suspension in mJ was cooled to about -tot' under stirring.
メチルリチウム（２８＋＋ｄ、ジエチルエーテル中１．
６Ｍ溶液＞１ｋｔＯ分間要しで江射器により添加した。Methyllithium (28++d, 1.0% in diethyl ether)
The 6M solution was added via injector for >1 ktO min.
得られた浴液ｔｌ−−１０℃で更に１５分間攪拌し、＋
２５℃に６時間加温した。生成物を氷／水（１５０ｄＪ
中で反応停止させ、ＭＤＯ中に抽出し、溶媒を蒸発させ
ることにより約４．２ｆの粗生成物を得た。The obtained bath liquid tl- was stirred for an additional 15 minutes at -10°C, +
It was heated to 25°C for 6 hours. The product was poured into ice/water (150 dJ
Approximately 4.2 f of the crude product was obtained by quenching the reaction in water, extracting into MDO, and evaporating the solvent.
代理人 弁理士 秋 沢 政 光他１名Agent: Patent attorney: Masaaki Aki, Hikaru Sawa, and 1 other person
Claims (6)
金属誘導体とを反応させることを特徴とする４−（６−
メトキシ−２−ナフチル）ブタン−２−オンを製造する
方法。(1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ 4-(6-
A method for producing methoxy-2-naphthyl)butan-2-one.
の形態をしている特許請求の範囲第（１）項記載の方法
。(2) The method according to claim (1), wherein the compound represented by formula (I) is in the form of its lithium salt.
、Ｈａｌはハロゲン、である）またはメチルリチウムが
含まれる特許請求の範囲第（１）または（２）項記載の
方法。(3) The method according to claim 1 or 2, wherein the methyl metal derivative includes CH_3MgHal (wherein Hal is a halogen) or methyllithium.
範囲第（１）〜（３）項のいずれか一つの項記載の方法
。(4) The method according to any one of claims (1) to (3), wherein the reaction is carried out in an inert organic solvent.
ｌであるときは還流温度にあるいはメチル金属誘導体が
メチルリチウムであるときは０〜５０℃に保持される特
許請求の範囲第（１）〜（４）項のいずれか一つの項記
載の方法。(5) The reaction temperature is CH_3MgHa when the methyl metal derivative is
The method according to any one of claims (1) to (4), wherein the temperature is maintained at reflux temperature when the methyl metal derivative is methyllithium, or at 0 to 50°C when the methyl metal derivative is methyllithium.
オン酸のリチウム塩とメチルリチウムとを反応させるこ
とを特徴とする４−（６−メトキシ−２−ナフチル）ブ
タン−２−オンを製造する方法。(6) 4-(6-methoxy-2-naphthyl)butan-2-one is produced by reacting a lithium salt of 3-(6'-methoxy-2'-naphthyl)propionic acid with methyllithium. How to manufacture.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8603777 | 1986-02-15 | ||
| GB868603777A GB8603777D0 (en) | 1986-02-15 | 1986-02-15 | Chemical process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62195343A true JPS62195343A (en) | 1987-08-28 |
| JPH0733345B2 JPH0733345B2 (en) | 1995-04-12 |
Family
ID=10593133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3229487A Expired - Lifetime JPH0733345B2 (en) | 1986-02-15 | 1987-02-14 | Method for producing compound |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPH0733345B2 (en) |
| CH (1) | CH670082A5 (en) |
| DK (1) | DK75387A (en) |
| ES (1) | ES2004224A6 (en) |
| GB (1) | GB8603777D0 (en) |
| GR (1) | GR870257B (en) |
| NL (1) | NL8700357A (en) |
| SE (1) | SE8700593L (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756851A (en) * | 1996-10-21 | 1998-05-26 | Albemarle Corporation | Production of nabumetone or precursors thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT338257B (en) * | 1975-01-08 | 1977-08-10 | Beecham Group Ltd | PROCESS FOR PRODUCING NEW NAPHTHALIN DERIVATIVES |
-
1986
- 1986-02-15 GB GB868603777A patent/GB8603777D0/en active Pending
-
1987
- 1987-02-13 NL NL8700357A patent/NL8700357A/en not_active Application Discontinuation
- 1987-02-13 DK DK75387A patent/DK75387A/en not_active Application Discontinuation
- 1987-02-13 CH CH53787A patent/CH670082A5/en not_active IP Right Cessation
- 1987-02-13 SE SE8700593A patent/SE8700593L/en not_active Application Discontinuation
- 1987-02-13 GR GR870257A patent/GR870257B/en unknown
- 1987-02-13 ES ES8700374A patent/ES2004224A6/en not_active Expired
- 1987-02-14 JP JP3229487A patent/JPH0733345B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CH670082A5 (en) | 1989-05-12 |
| GR870257B (en) | 1987-06-16 |
| JPH0733345B2 (en) | 1995-04-12 |
| SE8700593D0 (en) | 1987-02-13 |
| DK75387D0 (en) | 1987-02-13 |
| DK75387A (en) | 1987-08-16 |
| SE8700593L (en) | 1987-08-16 |
| GB8603777D0 (en) | 1986-03-19 |
| ES2004224A6 (en) | 1988-12-16 |
| NL8700357A (en) | 1987-09-01 |
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