JPS62195344A - Manufacture of novel intermediate - Google Patents
Manufacture of novel intermediateInfo
- Publication number
- JPS62195344A JPS62195344A JP3229587A JP3229587A JPS62195344A JP S62195344 A JPS62195344 A JP S62195344A JP 3229587 A JP3229587 A JP 3229587A JP 3229587 A JP3229587 A JP 3229587A JP S62195344 A JPS62195344 A JP S62195344A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- iii
- carried out
- compounds
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 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
- 239000002253 acid Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- GDZAZDIBXJWVQO-UHFFFAOYSA-N 1-(6-methoxynaphthalen-2-yl)butan-2-one Chemical compound C1=C(OC)C=CC2=CC(CC(=O)CC)=CC=C21 GDZAZDIBXJWVQO-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 150000007857 hydrazones Chemical class 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 229960004270 nabumetone Drugs 0.000 description 2
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
- -1 alkyl compound Chemical class 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
-
- 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
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (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】
〔産業上の利用分野〕
本発明は４−（６−メドキシー２−ナフチルＪブタンー
２−オンｔ−Ｓ造する方法及びその合成に有用な中間体
に関する、
〔従来の技術〕
米国特許第４０６１７７９号明細書は４−（６−メドキ
シー２−ナフチル）ブタン−２−オン〔ナブメトン（ｎ
ａｂｕｍｅｔｏｎｅＪ）及びリウマチ及び関節炎の症状
の治療におけるその用途全記載している。該化合物を製
造する多数の方法も記載されている。米国特許第４２２
１７４１号及び同第４２４７７０９号明細書はナブメト
２を製造する他の方法を記載している。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for preparing 4-(6-medoxy-2-naphthyl J-butan-2-one t-S) and intermediates useful for the synthesis. Technology] U.S. Pat. No. 4,061,779 describes 4-(6-medoxy-2-naphthyl)butan-2-one [nabumetone
abumetone J) and its use in the treatment of rheumatoid and arthritic conditions are fully described. A number of methods of making the compounds have also been described. US Patent No. 422
No. 1741 and No. 4,247,709 describe other methods of making nabumet 2.
ナブメトンを製造する他の方法が見い出されその方法は
ヒドラゾンの形成次いで加水分Ｓｔ−％倣とする。Another method of making nabumetone has been found, which involves the formation of a hydrazone followed by hydrolysis St-%.
従って本発明は式中
（式中ＨａｔはハロゲンであるＪ
の化合物と式■
Ｎ−ＮＲＩル２
Ｍ０Ｈ２００Ｈ３■
（式中Ｍはアルカリ金属でありａｌ及びＲ２は０１〜６
アルキルである）
の化合物とを反応させ次に酸加水分解を行うことよりな
る４−（６−メドキシー２−ナフチルｔｆタンー２−オ
ンを製造する方法を提供する。Therefore, the present invention provides a compound of the formula J (wherein Hat is a halogen) and a compound of the formula (1) N-NRI2 M0H200H3 (wherein M is an alkali metal and al and R2 are
A process for producing 4-(6-medoxy-2-naphthyl tf-tan-2-one) is provided, which comprises reacting a compound of 4-(6-medoxy-2-naphthyl tf-tan-2-one) with an alkyl compound, followed by acid hydrolysis.
Ｈａｔは好ましくは塩素でありセしてＭは好ましくはリ
チウムである。ａｌ及びＲ２は好ましくはともにメチル
である。Hat is preferably chlorine and M is preferably lithium. al and R2 are preferably both methyl.
反応は室温で不活性溶媒例えはテトラヒドロフラン中で
生ずる。The reaction takes place at room temperature in an inert solvent such as tetrahydrofuran.
反応は式［相］
Ｎ−Ｎル１ル２
式中の化合物の次の加水分解は室ｍ ｆｌｊえば２０〜
３０℃で−１げ塩酸／水を用いる酸乗件下で生ずる。The reaction is expressed by the formula [phase] N-N 1 2 The next hydrolysis of the compound in the formula is in the chamber
The reaction is carried out under acid conditions using −1-dihydrochloric acid/water at 30°C.
式（ＩＩ）の化合物は好都合にはアセトン及びＮ、Ｎ−
ジメチルヒドラジンからその場で製造される。The compound of formula (II) is conveniently prepared in acetone and N,N-
Manufactured in situ from dimethylhydrazine.
式中の化合物は周知である。The compounds in the formula are well known.
式［相］の化合物は新規であり本発明の様相を形成する
。The compounds of formula [phase] are new and form an aspect of the invention.
下記の実施例は本発明を説明する。 The following examples illustrate the invention.
実施例
【
その場で製造したアセトンのリチオＮ、Ｎ−ジメチルヒ
ドラゾン及び２−クロロメチル−６−メドキシナフタレ
ンからヒドラゾン（２）が定量的に製造されそして油と
して得られ九〔ヤマシタも「プル、ケム、ソサ、ジャパ
ン（Ｂｕｌｌ、Ｏｈｅｍ、８ｏｃ、ＪｐｎＪ５８．４０
７〜４０８（Ｌ９８５＋参照〕。EXAMPLE Hydrazone (2) was quantitatively prepared from lithio-N,N-dimethylhydrazone and 2-chloromethyl-6-medoxynaphthalene of acetone prepared in situ and obtained as an oil. , Kem, Sosa, Japan (Bull, Ohem, 8oc, JpnJ58.40
7-408 (see L985+).
ヒドラゾン（２）を室温で５Ｍ塩酸により処理して収率
９５％純度８０％（純粋収率７６チ２で生成物（３）を
得た。Hydrazone (2) was treated with 5M hydrochloric acid at room temperature to give product (3) in 95% yield and 80% purity (76% pure yield).
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 (10)
＿１＿〜＿６アルキルである） の化合物とを反応させ、次に式（III） ▲数式、化学式、表等があります▼（III） の中間体化合物を酸加水分解す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.▼(I) (Hal in the formula is a halogen) Compound and formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) ( In the formula, M is an alkali metal, and R_1 and R_2 are C
4-, which is characterized by reacting with a compound of formula (III) (which is alkyl from _1 to _6) and then subjecting the intermediate compound of formula (III) to acid hydrolysis.
A method for producing (6-methoxy-2-naphthyl)butan-2-one.
第（１）記項載の方法。(2) The method according to claim (1), wherein Hal in formula (I) is chlorine.
（１）又は（２）項記載の方法。(3) The method according to claim (1) or (2), wherein M in formula (II) is lithium.
第（１）〜（３）項の何れか一つの項記載の方法。(4) The method according to any one of claims (1) to (3), wherein R_1 and R_2 are methyl.
が不活性有機溶媒中で行われる特許請求の範囲第（１）
〜（４）項の何れか一つの項記載の方法。(5) Claim No. 1, wherein the reaction between the compound of formula (I) and the compound of formula (II) is carried out in an inert organic solvent.
The method described in any one of (4) to (4).
が室温で行われる特許請求の範囲第（１）〜（５）項の
何れか一つの項記載の方法。(6) The method according to any one of claims (1) to (5), wherein the reaction between the compound of formula (I) and the compound of formula (II) is carried out at room temperature.
式、化学式、表等があります▼（III） の化合物。(7) A compound of formula (III) where R_1 and R_2 are methyl ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III).
溶液中で行われる特許請求の範囲第（１）項記載の方法
。(8) The method according to claim (1), wherein the acid hydrolysis of the intermediate compound of formula (III) is carried out in an aqueous hydrochloric acid solution.
〜３０℃の温度で行われる特許請求の範囲第（８）項記
載の方法。(9) Acid hydrolysis of the intermediate compound of formula (III) at 20°C
A method according to claim 8, which is carried out at a temperature of -30<0>C.
リチウムでありＲ＿１及びＲ＿２がメチルである式（I
I）の化合物とを反応させ、次に塩酸水溶液中で式（II
I）の中間体化合物を酸加水分解することよりなり式（
I ）、（II）及び（III）の化合物が特許請求の範囲第
（１）項で規定されている４−（６−メトキシ−２−ナ
フチル）ブタン−２−オンを製造する方法。(10) Compounds of formula (I) where Hal is chlorine and compounds of formula (I) where M is lithium and R_1 and R_2 are methyl
I) and then reacted with the compound of formula (II) in an aqueous hydrochloric acid solution.
By acid hydrolyzing the intermediate compound of I), the formula (
A process for producing 4-(6-methoxy-2-naphthyl)butan-2-one, wherein the compounds I), (II) and (III) are defined in claim (1).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB868603778A GB8603778D0 (en) | 1986-02-15 | 1986-02-15 | Chemical process |
| GB8603778 | 1986-02-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS62195344A true JPS62195344A (en) | 1987-08-28 |
Family
ID=10593134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3229587A Pending JPS62195344A (en) | 1986-02-15 | 1987-02-14 | Manufacture of novel intermediate |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPS62195344A (en) |
| CH (1) | CH670084A5 (en) |
| DK (1) | DK75487A (en) |
| ES (1) | ES2004879A6 (en) |
| GB (1) | GB8603778D0 (en) |
| GR (1) | GR870258B (en) |
| NL (1) | NL8700358A (en) |
| SE (1) | SE465926B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4943579A (en) * | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3829586A1 (en) * | 1988-09-01 | 1990-03-22 | Bayer Ag | DISUBSTITUTED NAPHTHALINE, METHOD FOR THE PRODUCTION AND THEIR USE OF HERBICIDES |
| US5756851A (en) * | 1996-10-21 | 1998-05-26 | Albemarle Corporation | Production of nabumetone or precursors thereof |
| CU23844B1 (en) * | 2009-04-17 | 2012-10-15 | Ct De Neurociencias De Cuba | PROCEDURE FOR OBTAINING NEW DERIVATIVES OF NAFTALENE FOR THE LIVE DIAGNOSIS OF ALZHEIMER'S DISEASE |
-
1986
- 1986-02-15 GB GB868603778A patent/GB8603778D0/en active Pending
-
1987
- 1987-02-13 CH CH53687A patent/CH670084A5/en not_active IP Right Cessation
- 1987-02-13 ES ES8700375A patent/ES2004879A6/en not_active Expired
- 1987-02-13 SE SE8700594A patent/SE465926B/en unknown
- 1987-02-13 NL NL8700358A patent/NL8700358A/en not_active Application Discontinuation
- 1987-02-13 GR GR870258A patent/GR870258B/en unknown
- 1987-02-13 DK DK75487A patent/DK75487A/en unknown
- 1987-02-14 JP JP3229587A patent/JPS62195344A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4943579A (en) * | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
Also Published As
| Publication number | Publication date |
|---|---|
| NL8700358A (en) | 1987-09-01 |
| DK75487D0 (en) | 1987-02-13 |
| SE465926B (en) | 1991-11-18 |
| ES2004879A6 (en) | 1989-02-16 |
| SE8700594L (en) | 1987-08-16 |
| CH670084A5 (en) | 1989-05-12 |
| GR870258B (en) | 1987-06-16 |
| DK75487A (en) | 1987-08-16 |
| SE8700594D0 (en) | 1987-02-13 |
| GB8603778D0 (en) | 1986-03-19 |
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