JPH0477452A - Production of cyclooctane derivative - Google Patents
Production of cyclooctane derivativeInfo
- Publication number
- JPH0477452A JPH0477452A JP18964990A JP18964990A JPH0477452A JP H0477452 A JPH0477452 A JP H0477452A JP 18964990 A JP18964990 A JP 18964990A JP 18964990 A JP18964990 A JP 18964990A JP H0477452 A JPH0477452 A JP H0477452A
- Authority
- JP
- Japan
- Prior art keywords
- pref
- lithium
- cyclooctanone
- compound
- cyclooctane
- 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 7
- 125000000640 cyclooctyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 title 1
- IIRFCWANHMSDCG-UHFFFAOYSA-N cyclooctanone Chemical compound O=C1CCCCCCC1 IIRFCWANHMSDCG-UHFFFAOYSA-N 0.000 claims abstract description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims abstract description 9
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000002642 lithium compounds Chemical class 0.000 claims abstract description 7
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229940014800 succinic anhydride Drugs 0.000 claims abstract description 6
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract 3
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000001938 cyclooctanes Chemical class 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 4
- 150000003180 prostaglandins Chemical class 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 abstract description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 abstract description 2
- MEOKEWOGEQTBTJ-UHFFFAOYSA-N 7-(2,5-dioxocyclopentyl)heptanoic acid Chemical compound OC(=O)CCCCCCC1C(=O)CCC1=O MEOKEWOGEQTBTJ-UHFFFAOYSA-N 0.000 abstract 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 abstract 1
- 229910052744 lithium Inorganic materials 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- GCWCFCODTCPSLE-UHFFFAOYSA-N 4-oxo-4-(2-oxocyclooctyl)butanoic acid Chemical compound OC(=O)CCC(=O)C1CCCCCCC1=O GCWCFCODTCPSLE-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- -1 dioxocyclopentyl Chemical group 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000002194 synthesizing effect Effects 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【発明の詳細な説明】
皮！上夏机■分■
本発明はシクロオクタノン誘導体の新規製造方法に関し
、さらに詳しくはプロスタグランジン類に含まれるシク
ロペンテニルへブタン酸誘導体の製造における重要中間
体である７−（２，５−ジオキソシクロペンチル）へブ
タン酸の製造中間体として有用なシクロオクタン誘導体
の新規製造方法に関する。[Detailed Description of the Invention] Skin! The present invention relates to a new method for producing cyclooctanone derivatives, and more specifically, 7-(2,5- The present invention relates to a new method for producing cyclooctane derivatives useful as intermediates for producing dioxocyclopentyl)hebutanoic acid.
従来夏技血
プロスタグランジン類の合成は多くの方法が知られてい
るが、従来の方法はいずれも合成工程が長く、また合成
操作が煩雑である（例えばＡｇｒｉｃ。Many methods are known for synthesizing prostaglandins, but all of the conventional methods involve long synthesis steps and complicated synthesis operations (for example, Agric.
Ｂｉｏｌ−Ｃｈｅｗ、、 ３３＋ １０７８（１９６９
）； Ｊ、Ａｍ、 Ｃｈｅｗ、 Ｓｏｃ、。Biol-Chew, 33+ 1078 (1969
); J, Am, Chew, Soc.
、］、 ５６７５（１９６９）； １ｂｉｄ、
９２． ２５８６（１９７０）； Ｃｈｅｗ。, ], 5675 (1969); 1bid,
92. 2586 (1970); Chew.
Ｐｈａｒｓ、Ｂｕｌｌ、、 １７．４０８（１９６９）
参照）という問題がある。一方、７−（２，５−ジオキ
ソシクロペンチル）へブタン酸を原料として用いること
により、２〜３段階で高収率にプロスタグランジン類で
あるシクロペンテニル誘導体が合成される（例えば、Ｃ
ｈｅｓ、Ｌｅｔｔ、、 １９Ｂ旦＋ １４３；
Ｂｕｌｌ、 Ｃｈｅｗ、 Ｓｏｃ、Ｊｐｎ、。Phars, Bull, 17.408 (1969)
(see). On the other hand, by using 7-(2,5-dioxocyclopentyl)hebutanoic acid as a raw material, cyclopentenyl derivatives, which are prostaglandins, can be synthesized in high yield in 2 to 3 steps (for example, C
hes, Lett,, 19Bdan + 143;
Bull, Chew, Soc, Jpn.
■、 ２４０１（１９８Ｂ）： １ｂｉｄ、 ６１．２
８５９（１９８Ｂ）参照）。■, 2401 (198B): 1 bid, 61.2
859 (198B)).
また、シクロオクタン誘導体である４−（２−オキソシ
クロオクチル）−４−オキソブタン酸とルイス酸との反
応によっても７−（２，５−ジオキソシクロペンチル）
へブタン酸が１段階で製造できるが、？−（２，５−ジ
オキソシクロペンチル）へブタン酸の合成原料であるシ
クロオクタン誘導体の製造方法は、化学的に不安定なエ
ナミンを経由することから、工業上有利な方法とは言え
なかった。7-(2,5-dioxocyclopentyl) can also be produced by the reaction of 4-(2-oxocyclooctyl)-4-oxobutanoic acid, a cyclooctane derivative, with Lewis acid.
Hebutanoic acid can be produced in one step, but? The method for producing a cyclooctane derivative, which is a raw material for the synthesis of -(2,5-dioxocyclopentyl)hebutanoic acid, is not an industrially advantageous method because it involves the use of chemically unstable enamines.
が ” しようと る
式（１）、
で示されるシクロオクタン誘導体の、工業上有利な製造
方法を開発することをｖｌ、題とする。The purpose of the present invention is to develop an industrially advantageous method for producing a cyclooctane derivative represented by formula (1).
ｉ ”° るための
本研究者らは前記課題を解決すべく鋭意研究を重ねた結
果、安価なシクロオクタノンを、リチウム化合物の存在
下で無水コハク酸と反応させることにより１段階で式（
１）
で示されるシクロオクタン誘導体が製造できることを見
出し、この発明に基づいて本発明を完成するに到った。As a result of intensive research to solve the above problem, the researchers found that by reacting inexpensive cyclooctanone with succinic anhydride in the presence of a lithium compound, the formula (
1) It was discovered that the cyclooctane derivative shown in the following can be produced, and the present invention was completed based on this invention.
本発明に使用するリチウム化合物としては、リチウムジ
イソプロピルアミド、ｎ−ブチルリチウム、５ｅｃ−ブ
チルリチウム、ｔｅｒｔ−ブチルリチウム、あるいはメ
チルリチウム等が挙げられるが、好ましくはリチウムジ
イソプロピルアミドである。Examples of the lithium compound used in the present invention include lithium diisopropylamide, n-butyllithium, 5ec-butyllithium, tert-butyllithium, and methyllithium, but lithium diisopropylamide is preferred.
アルキルリチウムは、ジイソプロピルアミン存在下に用
いるとよい。リチウム化合物の使用蓋は、シクロオクタ
ノンに対して０．５〜２モル倍、好ましくは０．７５〜
１．２５倍である。無水コハク酸の使用量は、シクロオ
クタノンに対して０．５〜３モル倍、好ましくは０．７
５〜１．２５倍である。反応温度は一８０℃〜２５°Ｃ
の範囲が好ましく、より好ましくは、−８０℃〜０℃の
範囲である。反応時間は、１０分〜２４時間が適当であ
るが、好ましくは３０分〜１２時間の範囲が適当である
。Alkyllithium is preferably used in the presence of diisopropylamine. The amount of lithium compound to be used is 0.5 to 2 times the mole of cyclooctanone, preferably 0.75 to 2 times the mole of cyclooctanone.
It is 1.25 times. The amount of succinic anhydride used is 0.5 to 3 times the mole of cyclooctanone, preferably 0.7 times.
It is 5 to 1.25 times. Reaction temperature is -80℃~25℃
It is preferably in the range of -80°C to 0°C. The reaction time is suitably 10 minutes to 24 hours, preferably 30 minutes to 12 hours.
溶媒としては、テトラヒドロフラン、ジエチルエーテル
、あるいはジメトキシエタン等のエーテル系の溶媒が挙
げられるが、これらは単独あるいは適宜混合して用いる
ことができる。Examples of the solvent include ether solvents such as tetrahydrofuran, diethyl ether, and dimethoxyethane, and these can be used alone or in an appropriate mixture.
なお、本発明の反応は、アルゴンや窒素など不活性ガス
雰囲気下に行なうのが好ましい。Note that the reaction of the present invention is preferably carried out under an atmosphere of an inert gas such as argon or nitrogen.
１隻■ 以下、本発明を実施例により具体的に説明する。1 ship■ Hereinafter, the present invention will be specifically explained with reference to Examples.
ジイソプロピルアミン（１１，４９ｇ ： ０．１２３
５＋＋＋ｏｌ）をＴＨＦ（８０ｍｌ）に溶解し、−７８
℃で攪拌した。ｎ−ブチルリチウム（１，３Ｍ、 ９５
ｍ１ ＝ ０．１２３５ｍｏｌ）を１０分間かけて滴下
した。滴下終了後３０分間攪拌した後、シクロオクタノ
ン（１４ｇ：０．１１１ｓｏｌ）のＴＨＦ溶液（１２０
ｍｌ）を滴下した。Diisopropylamine (11,49g: 0.123
5+++ol) was dissolved in THF (80 ml), -78
Stir at ℃. n-Butyllithium (1,3M, 95
m1 = 0.1235 mol) was added dropwise over 10 minutes. After stirring for 30 minutes after the dropwise addition, a THF solution of cyclooctanone (14 g: 0.111 sol) (120
ml) was added dropwise.
さらに３０分間攪拌した後、無水コハク酸（１１，１１
ｇ ： ０．１１１ｓｏｌ）のＴＨＦ溶液（１８０ｍｌ
）を滴下した。−夜攪拌後、氷水（１０１００Ｏ）を加
えた。分層した無機層をエーテル（３００ａ＋１）で洗
浄した。After stirring for an additional 30 minutes, succinic anhydride (11,11
g: 0.111 sol) in THF solution (180 ml
) was added dropwise. - After stirring overnight, ice water (10100O) was added. The separated inorganic layer was washed with ether (300a+1).
塩酸により、ｐＨ２に調整し、酢酸エチル（２５゜卸ｌ
、２回）抽出した。抽出液を水（２５０ｍｌ、２回）、
飽和食塩水（２５０ｍｌ、２回）で洗浄し、無水硫酸マ
グネシウムにより乾燥した。減圧下、溶媒を留去し、４
−（２−オキソシクロオクチル）４−オキソブタン酸（
１５，５９ｇ、 ６２％）を得た。Adjust the pH to 2 with hydrochloric acid, add ethyl acetate (25°
, twice). The extract was mixed with water (250 ml, twice),
It was washed with saturated brine (250 ml, twice) and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and 4
-(2-oxocyclooctyl)4-oxobutanoic acid (
15.59 g, 62%) was obtained.
光亙■臥！
本発明によれば、上記のように工業的に入手容易な原料
を用いることにより、シクロオクタン誘導体をシクロオ
クタノンから１段階で効率よく製造することができる。Kouyo■wo! According to the present invention, a cyclooctane derivative can be efficiently produced from cyclooctanone in one step by using industrially easily available raw materials as described above.
Claims (1)
コハク酸と反応させることを特徴とする、式（１） ▲数式、化学式、表等があります▼（１） で示されるシクロオクタン誘導体の製造方法。 ２、リチウム化合物が、リチウムジイソプロピルアミド
、ｎ−ブチルリチウム、ｓｅｃ−ブチルリチウム、ｔｅ
ｒｔ−ブチルリチウム、およびメチルリチウムの少なく
とも一種である請求項１記載の製造方法。[Claims] 1. A compound characterized by reacting cyclooctanone with succinic anhydride in the presence of a lithium compound, represented by formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1) A method for producing a cyclooctane derivative. 2. The lithium compound is lithium diisopropylamide, n-butyllithium, sec-butyllithium, te
The manufacturing method according to claim 1, which is at least one of rt-butyllithium and methyllithium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18964990A JPH0477452A (en) | 1990-07-18 | 1990-07-18 | Production of cyclooctane derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18964990A JPH0477452A (en) | 1990-07-18 | 1990-07-18 | Production of cyclooctane derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0477452A true JPH0477452A (en) | 1992-03-11 |
Family
ID=16244853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18964990A Pending JPH0477452A (en) | 1990-07-18 | 1990-07-18 | Production of cyclooctane derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0477452A (en) |
-
1990
- 1990-07-18 JP JP18964990A patent/JPH0477452A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH07188069A (en) | Manufacturing of alkylcyclopentadien | |
| JPH0477452A (en) | Production of cyclooctane derivative | |
| JP4418048B2 (en) | Process for producing 13-cis-retinoic acid | |
| JP2004161702A (en) | METHOD FOR PRODUCING gamma-JASMOLACTONE | |
| JPS58134092A (en) | Theobromine derivative | |
| CN109096324B (en) | Synthesis method and application of dialkyl acyl germanium chloride | |
| JPS6222732A (en) | 1,1-(3-ethylphenyl)phenylethylene | |
| JPH0348633A (en) | Chain terpene compound | |
| JPS62298547A (en) | Production of 2-cyclopentenone derivative | |
| JPH02282376A (en) | Production of cis-7-decen-4-olide | |
| JPH02250845A (en) | Production of 3-(4-fluorophenyl)propionaldehyde | |
| JPS6126893B2 (en) | ||
| JP2000212125A (en) | Production of fluorine-containing carboxylic acid derivative | |
| JPH02101037A (en) | Production of 3-hydroxy-4-phenyl-2-butanone | |
| JPH06321831A (en) | Production of 1-substituted 1,4-dihydroxy-2-cyclopentenone derivative | |
| JPH09295963A (en) | Production of d-acetylthioisobutyric acid | |
| JPH02311471A (en) | Gamma-alkyl-gamma-phenylsulfonyl-alpha,beta-unsaturated butyrolactone | |
| JPH06199771A (en) | Benzaldehyde having substituent group at 2,3 and 4 position and it derivative | |
| JPS5819658B2 (en) | Production method of γ-damascone | |
| JPS58110559A (en) | 1-(substituted naphthyl)-2-sulfonyloxy-1-alkanone | |
| JP2004161614A (en) | beta-SUBSTITUTED-gamma-BUTYROLACTONES AND METHOD FOR PRODUCING THE SAME | |
| JPH0346447B2 (en) | ||
| JPH0434552B2 (en) | ||
| JPS6032788A (en) | Novel yohimbinone analog, its preparation and use | |
| JPH02250848A (en) | Cyclooctane derivative and use thereof |