CS239895B1 - Processing of 1-hydroxylcyclopenty-(2-chlorphenyl) ketone - Google Patents
Processing of 1-hydroxylcyclopenty-(2-chlorphenyl) ketone Download PDFInfo
- Publication number
- CS239895B1 CS239895B1 CS841716A CS171684A CS239895B1 CS 239895 B1 CS239895 B1 CS 239895B1 CS 841716 A CS841716 A CS 841716A CS 171684 A CS171684 A CS 171684A CS 239895 B1 CS239895 B1 CS 239895B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- ketone
- chlorophenyl
- hydroxycyclopentyl
- substance
- bromocyclopentyl
- Prior art date
Links
- 150000002576 ketones Chemical class 0.000 title 1
- ZQMPBNBKHMEDEA-UHFFFAOYSA-N bis[2-chloro-3-(1-hydroxycyclopentyl)phenyl]methanone Chemical compound OC1(CCCC1)C=1C(=C(C=CC=1)C(=O)C1=C(C(=CC=C1)C1(CCCC1)O)Cl)Cl ZQMPBNBKHMEDEA-UHFFFAOYSA-N 0.000 claims abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- DDVNLGGCSRULIL-UHFFFAOYSA-N (1-bromocyclopentyl)-(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)C1(Br)CCCC1 DDVNLGGCSRULIL-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000002904 solvent Substances 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 5
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003533 narcotic effect Effects 0.000 abstract description 2
- -1 1-hydroxycyclopentyl Chemical group 0.000 abstract 1
- 230000001476 alcoholic effect Effects 0.000 abstract 1
- 229910052783 alkali metal Inorganic materials 0.000 abstract 1
- 150000001340 alkali metals Chemical class 0.000 abstract 1
- 238000000638 solvent extraction Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- GRBWBBBWQYSRBG-UHFFFAOYSA-N bis[3-(1-bromocyclopentyl)-2-chlorophenyl]methanone Chemical compound ClC1=C(C(=O)C=2C(=C(C=CC=2)C2(Br)CCCC2)Cl)C=CC=C1C1(Br)CCCC1 GRBWBBBWQYSRBG-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
l-hydroxycyklopentyl-/2-chlorfenyl/- -keton je klíčový meziprodukt pro přípravu hydrochloridu 2-/-2chlorfenyl/-2-methylaminocyklohexanonu. Tato látka se pod generickým názvem Ketefflin používá ve farmacii v injekční formě jako ultrakrátké narkotikum. 1-hydroxycyklopentyl l-/2-chlorfenyl/-keton se připravuje tak, že se 1-bromcyklopentyl-/2-chlorfenyl/-keton nechá reagovat ve vodně alkoholickém roztoku s hydroxydem alkalického kovu při 20 až 30 °C. Látka se po extrakci rozpouštědlem, které se nemísí s vodou a zahuštěním získá ve výtěžku 98 % th.1-hydroxycyclopentyl- (2-chlorophenyl) - ketone is a key intermediate for preparation 2- (2-chlorophenyl) -2-methylaminocyclohexanone hydrochloride. This substance is under generic Ketefflin used in pharmacy injectable as an ultrashort narcotic. 1-hydroxycyclopentyl 1- (2-chlorophenyl) ketone is prepared by 1-bromocyclopentyl (2-chlorophenyl) ketone he reacts in an aqueous alcoholic solution with hydroxyde alkali metal at 20 to 30 ° C. Substance after solvent extraction, which is not mixed with water and concentration in a yield of 98% th.
Description
1-hydroxycyklopentyl-/2-chlorfeny l/-keton je jedním z klíčových meziproduktů pro přípravu hydrochloridu 2-/2-chlorfenyl/-2-methylaminocyklohexanonu. Tato látka se používá pod generickým názvem Ketamin ve farmacií ve formě injekci jako ultrakrátké narkotikum.1-Hydroxycyclopentyl- (2-chlorophenyl) -ketone is one of the key intermediates for the preparation of 2- (2-chlorophenyl) -2-methylaminocyclohexanone hydrochloride. This substance is used under the generic name Ketamine in pharmacy as an injection as an ultra-short narcotic.
C.L.Stevens v americkém patentovém spisu 3254124/1966 popisuje přípravu epoxyetheru z 1-bromcyklopentyl-/2-chlorfenyl/-ketonu reakcí s methylátem sodným v bezvodém metanolu ve výtěžku 96% th.C. L. Stevens in U.S. Pat. No. 3,254,124 / 1966 describes the preparation of an epoxy ether from 1-bromocyclopentyl- (2-chlorophenyl) ketone by reaction with sodium methylate in anhydrous methanol in a yield of 96% th.
C.L.Stevens a S.J.Dykstra v lJ.Am.Soc.76, 4402/1954 popisuje metanolysu epoxyetheru za přítomnosti katalitického množství kys.sírové. Reakční směs se vaří pod,zpětným chladičem 1,5hod. a získá se tak hydroxyketal ve výtěžku 95% th. Tato látka se pak hydrolýsuje tak, že se vaří ve vodně metanolickém roztoku za katalysy kys.sírové. Získá se tak 1-hydroxycyklopentyl-/2-cnlorfenyl/-keton ve výtěžku 75%th. Tento jediný v literatuře popsaný postup pro přípravu žádané látky je z hlediska technologického příliš složitý a neekonomický. Celková vypočtená výtěžnost od výchozí suroviny 1-bromcyklopentyl-/2-chlorfenyl/-ketonu k žádané látce činí cca 68% th. a obsahuje 3 syntetické stupně. Postup je Časově náročný a technologicky komplikovaný.C. L. Stevens and S. J. Dykstra in J. Am. Soc. The reaction mixture was refluxed for 1.5 hours. to give the hydroxyketal in a yield of 95% th. This material is then hydrolyzed by boiling in aqueous methanolic solution to form sulfuric acid catalysis. There was thus obtained 1-hydroxycyclopentyl- (2-chlorophenyl) ketone in a yield of 75% th. This only procedure described in the literature for the preparation of the desired substance is too complex and uneconomical in terms of technology. The total calculated yield from the starting material 1-bromocyclopentyl- (2-chlorophenyl) ketone to the desired substance is about 68% th. and contains 3 synthetic steps. The procedure is time-consuming and technologically complicated.
Nedostatky literárního postupu řeší postup podle vynálezu, který spočívá v tom, že se výchozí suroviny 1-bromcyklopentyl-/2-chlorfenyl/-keton rozpustí v etanolu a k tomuto roztoku se při 20-30°přikape ekvimolárni množství vodného roztoku sodného, nebo draselného hydroxydu. Po naředění reakční směsi vodou se z vodně etanolického roztoku extrahuje 1-hydroxycyklopentyl-/2-chlorfenyl/-keton ether«mnebo jiným s vodou se nemísícim rozpouštědlem. Etherický extrakt se po odděleniThe drawbacks of the literature process are solved by the process according to the invention which consists in dissolving the starting material 1-bromocyclopentyl- (2-chlorophenyl) ketone in ethanol and adding an equimolar amount of aqueous sodium or potassium hydroxide solution dropwise at 20-30 °. . After diluting the reaction mixture with water, 1-hydroxycyclopentyl- (2-chlorophenyl) ketone ether or another water-immiscible solvent is extracted from the aqueous ethanol solution. The ether extract is separated after separation
239 89S a vysušení vhodným sušídlem zfiltruje a zahustí ve vakuu. Zbylý olej je žádaná látka a získá se ve výtěžku 98% th. Takto získaný produkt je vhodný pro další zpracováni.239 89S and drying with a suitable desiccant is filtered and concentrated in vacuo. The residual oil is the desired compound and is obtained in a yield of 98% th. The product thus obtained is suitable for further processing.
jeho čistotě se lze přesvědčit TLC chromatografií.its purity can be assured by TLC chromatography.
Metoda přípravy je zvláště vhodná z hlediska technologického proto, že se žádaná látka může připravovat v libovolném měřítku.The method of preparation is particularly suitable from a technological point of view because the desired substance can be prepared on any scale.
Pří klad provedeníExecution example
1-bromcyklopentyl-/-2-chlorfenyl/-keton /275,6 g/ se rozpustí v 360 ml etanolu a za mícháni a chlazeni se k roztoku přikape vodný roztok hydroxydu sodného. Teplota směsi při přidáváni nesmi překročit 30°.1-Bromocyclopentyl - [- 2-chlorophenyl] ketone (275.6 g) was dissolved in 360 ml of ethanol and an aqueous sodium hydroxide solution was added dropwise to the solution with stirring and cooling. The temperature of the mixture during addition must not exceed 30 °.
Po skončeném přidávání roztoku hydroxydu se reakční směs nalije do 3 l vody. Tato směs se vytřepe etherem, etherický roztok se vysuší bezvodým síranem sodným a po filtraci se etherický roztok ve vakuu zahusti.After the addition of the hydroxyde solution is complete, the reaction mixture is poured into 3 L of water. The mixture was shaken with ether, the ether solution was dried over anhydrous sodium sulfate, and after filtration, the ether solution was concentrated in vacuo.
Zbylý olej /212 g 98 %th/ je možno bez dalšího čištění použit k dalšímu zpracování. Látka je chromatógraficky j ednotná.The remaining oil (212 g 98% th) can be used for further processing without further purification. The substance is chromatographically uniform.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS841716A CS239895B1 (en) | 1984-03-12 | 1984-03-12 | Processing of 1-hydroxylcyclopenty-(2-chlorphenyl) ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS841716A CS239895B1 (en) | 1984-03-12 | 1984-03-12 | Processing of 1-hydroxylcyclopenty-(2-chlorphenyl) ketone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS171684A1 CS171684A1 (en) | 1985-06-13 |
| CS239895B1 true CS239895B1 (en) | 1986-01-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS841716A CS239895B1 (en) | 1984-03-12 | 1984-03-12 | Processing of 1-hydroxylcyclopenty-(2-chlorphenyl) ketone |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS239895B1 (en) |
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1984
- 1984-03-12 CS CS841716A patent/CS239895B1/en unknown
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| Publication number | Publication date |
|---|---|
| CS171684A1 (en) | 1985-06-13 |
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