CH345885A - Process for the preparation of 1-ketocyclooctyl-2-acetic acid - Google Patents
Process for the preparation of 1-ketocyclooctyl-2-acetic acidInfo
- Publication number
- CH345885A CH345885A CH345885DA CH345885A CH 345885 A CH345885 A CH 345885A CH 345885D A CH345885D A CH 345885DA CH 345885 A CH345885 A CH 345885A
- Authority
- CH
- Switzerland
- Prior art keywords
- parts
- acetic acid
- ketocyclooctyl
- preparation
- solution
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000003839 salts Chemical class 0.000 claims description 6
- -1 alkali metal cyanides Chemical class 0.000 claims description 5
- 238000005956 quaternization reaction Methods 0.000 claims description 4
- BJLAFTQXYOGRDH-UHFFFAOYSA-N 2-(2-oxocyclooctyl)acetonitrile Chemical compound C(#N)CC1C(CCCCCC1)=O BJLAFTQXYOGRDH-UHFFFAOYSA-N 0.000 claims description 3
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- RAJTUUSARANEAK-UHFFFAOYSA-N 2-(aminomethyl)cyclooctan-1-one Chemical group NCC1CCCCCCC1=O RAJTUUSARANEAK-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- ARYCMVUVDJSGNS-UHFFFAOYSA-N 2-[(dimethylamino)methyl]cyclooctan-1-one Chemical compound CN(C)CC1CCCCCCC1=O ARYCMVUVDJSGNS-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- KPJPHPFMCOKUMW-UHFFFAOYSA-N iodomethane Chemical compound I[CH2] KPJPHPFMCOKUMW-UHFFFAOYSA-N 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- IIRFCWANHMSDCG-UHFFFAOYSA-N cyclooctanone Chemical compound O=C1CCCCCCC1 IIRFCWANHMSDCG-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 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
- 238000006683 Mannich reaction Methods 0.000 description 1
- 235000003893 Prunus dulcis var amara Nutrition 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000008845 cholagoga Substances 0.000 description 1
- 229940124571 cholagogue Drugs 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- VRZVPALEJCLXPR-UHFFFAOYSA-N ethyl 4-methylbenzenesulfonate Chemical compound CCOS(=O)(=O)C1=CC=C(C)C=C1 VRZVPALEJCLXPR-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 150000004721 gamma keto acids Chemical class 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von 1-Ketocyclooktyl-2-essigsäure
Es wurde gefunden, dass man die bisher unbekannte 1 -Ketocyclooktyl-2-essigsäure in einfacher Weise erhält, wenn man tertiäre 2-Aminomethyl cyclooktanone-(1) in Form ihrer Salze oder ihrer Quaternisierungsprodukte mit Alkalicyaniden umsetzt und das erhaltene 2-(Cyanomethyl-)cyclooktanon-(1) verseift.
Die Umsetzungsfolge lässt sich im Falle der Verwendung des 2-Dimethylaminomethylcyclooktanon (2)-jodmethylats und von Natriumcyanid als Ausgangsstoffen wie folgt wiedergeben:
EMI1.1
Die tertiären 2-Aminomethylcyclooktanone-( 1) lassen sich nach dem Prinzip der sogenannten Mannich-Reaktion durch Umsetzen von Cyclooktanon mit Formaldehyd und sekundären Aminen, wie Dimethyl-, Diäthyl-, Methyläthylamin, Pyrrolidin, Piperidin oder Morpholin, leicht herstellen. Aus diesen tertiären Aminen erhält man die für das vorliegende Verfahren als Ausgangsstoffe dienenden Salze oder Quaternierungsprodukte in an sich bekannter Weise durch Umsetzen z. B. mit Chlor-, Brom- oder Jodwasserstoff bzw. mit Methyl- oder Äthyljodid oder -bromid, mit Dimethylsulfat oder p-Toluolsulfonsäureäthylester.
Die Umsetzung der Salze bzw. Quaternisierungsprodukte der Mannich-Basen des Cyclooktanons mit Alkalicyaniden wird zweckmässig in wässriger oder wässrig-alkoholischer Lösung ausgeführt. Die Bildung des Nitrils wird durch Erwärmen, z. B. auf 50 bis 800 C, und durch Verwendung eines tÇber- schusses von Natrium- oder Kaliumcyanid gefördert.
Die dabei gemäss obigem Reaktionsschema freiwerdenden Amine kann man, wenn sie unter den Um setzungsbedingungen flüchtig sind, in verdünnter Säure auffangen, andernfalls gewinnt man sie z. B. durch fraktionierte Destillation des Reaktionsgemisches zurück.
Das erhaltene 2-(Cyanomethyl-)cyclooktanon-( 1) ist eine wasserunlösliche, farblose, schwach nach bitteren Mandeln riechende Flüssigkeit, die man durch Destillation reinigen kann. Sie zeigt die für ein y-Ketonitril typischen Eigenschaften.
Die Verseifung dieses Nitrils bewirkt man zweckmässigerweise durch Erhitzen mit wässriger Alkalilauge. Aus der erhaltenen Lösung ihres Alkalisalzes kann man die 1-Ketocyclooktyl-2-essigsäure durch Neutralisieren, z. B. mit Salze der Schwefelsäure, gewinnen.
Die so erhaltene neue y-Ketosäure und ihre wasserlöslichen Salze besitzen gallentreibende Wirkung, die sich bei Versuchen an Meerschweinchen als erheblich grösser erwies als die der Dehydrocholsäure.
Die in den Beispielen genannten Teile sind Gewichtsteile.
Beispiel 1
146 Teile 2-Dimethylaminomethylcyclooktanon (1) -jodmethylat (Schmp. 182-184"C, hergestellt durch Umsetzen von 91 Teilen 2-Dimethylaminomethylcyclooktanon-(1) mit 106 Teilen Methyljodid in Essigsäureäthylester) werden in eine Lösung von 66 Teilen Natriumcyanid in 1320 Teilen Wasser unter Rühren eingetragen. Man erwärmt die zunächst klare Lösung etwa 100 Minuten auf 65 bis 700 C, wobei Trimethylamin entweicht und sich das 2-Cyanomethylcyclooktanon-(1) als Öl ausscheidet. Dann lässt man erkalten, trennt das Ö1 ab, extrahiert die wässrige Schicht mit Äther, vereinigt den Atherextrakt mit dem Öl, trocknet mit Natriumsulfat und verdampft den Äther.
Der Rückstand ergibt bei der Destillation 68 Teile 2-Cyanomethylcyclooktanon- (1) vom Kr,, = 106 bis 1070 C. Das Ketonitril lässt sich durch sein Semicarbazon charakterisieren, das bei 127 bis 128 C schmilzt.
68 Teile 2-Cyanomethylcyclooktanon-(1) werden mit einer Lösung von 115 Teilen Kaliumhydroxyd in 460 Teilen Wasser 7 bis 8 Stunden unter Rückfluss zum Sieden erhitzt. Nach dem Erkalten entfernt man verseifte Anteile durch Extrahieren mit Äther, worauf man die wässrig-alkalische Schicht mit Salzsäure bis zur kongosauren Reaktion versetzt. Die freie 1-Ketocyclooktyl-2-essigsäure scheidet sich im allgemeinen zunächst als Ö1 aus. Man extrahiert die wässrige Schicht mit Ather, vereinigt den Ather- extrakt mit dem Öl, trocknet über Natriumsulfat und verdampft den Äther. Man erhält 67 Teile 1 -Keto- cyclooktyl-2-essigsäure, die nach dem Umkristallisieren aus Cyclohexan bei 71 bis 720 C schmilzt.
Ihr Phenylhydrazon zeigt den Schmp. 109 bis 110 C (unter Zersetzung).
Beispiel 2
97 Teile 2- Trimethylammoniummethylcyclo- oktanon-(l)-methylsulfat (Schmp. 99 C, hergestellt durch Umsetzen von 73 Teilen 2-Dimethylaminomethylcyclooktanon-(1) mit 252 Teilen Dimethylsulfat in trockenem Tetrahydrofuran unter Zusatz kleiner Mengen Eisessig bei 10-15" C) werden mit der Lösung von 48 Teilen Natriumcyanid in 950 Teilen Wasser wie im Beispiel 1 umgesetzt. Man erhält 36 Teile 2-Cyanomethylcyclooktanon-(1) und daraus 36 Teile 1 -Ketocyclooktyl-2-essigsäure.
Beispiel 3
44 Teile 2-Dimethylaminomethylcyclooktanon (1)-hydrochlorid (Schmp. 138-139"C unter Zersetzung, hergestellt durch Einleiten von trockenem Chlorwasserstoff in eine Lösung von 40 Teilen 2-Dimethylaminomethylcyclooktanon-(1) in 160 Teilen absolutem Äthanol unter Kühlung und Ausfällen mit absolutem Äther) werden mit einer Lösung von 30 Teilen Natriumcyanid in 600 Teilen Wasser wie im Beispiel 1 umgesetzt. Nach der Verseifung des Nitrils erhält man 18 Teile 1 -Ketocyclooktyl-2-essig- säure.
Beispiel 4
108 Teile 2-Piperidinomethylcyclooktanon-( 1)jodmethylat (Schmp. 126-128" C, hergestellt durch Erwärmen einer Lösung von 87 Teilen 2-Piperidinomethylcyclooktanon-(1) in 160 Teilen absolutem Äthanol mit 82 Teilen Methyljodid und Ausfällen mit absolutem Äther) werden mit einer Lösung von 45 Teilen Natriumcyanid in 900 Teilen Wasser wie im Beispiel 1 umgesetzt. Nach der Verseifung des Nitrils erhält man 30 Teile 1-Ketocyclooktyl-2-essig- saure.
Process for the preparation of 1-ketocyclooctyl-2-acetic acid
It has been found that the hitherto unknown 1-ketocyclooctyl-2-acetic acid is obtained in a simple manner if tertiary 2-aminomethyl cyclooktanone- (1) in the form of their salts or their quaternization products are reacted with alkali metal cyanides and the 2- (cyanomethyl- ) saponified cyclooctanone- (1).
In the case of using 2-dimethylaminomethylcyclooctanone (2) iodomethylate and sodium cyanide as starting materials, the reaction sequence can be reproduced as follows:
EMI1.1
The tertiary 2-aminomethylcyclooktanones- (1) can be easily prepared according to the principle of the so-called Mannich reaction by reacting cyclooctanone with formaldehyde and secondary amines such as dimethyl, diethyl, methylethylamine, pyrrolidine, piperidine or morpholine. The salts or quaternization products used as starting materials for the present process are obtained from these tertiary amines in a manner known per se by reacting, for. B. with chlorine, bromine or hydrogen iodide or with methyl or ethyl iodide or bromide, with dimethyl sulfate or ethyl p-toluenesulfonate.
The reaction of the salts or quaternization products of the Mannich bases of cyclooctanone with alkali metal cyanides is expediently carried out in an aqueous or aqueous-alcoholic solution. The formation of the nitrile is achieved by heating, e.g. B. to 50 to 800 C, and promoted by using an excess of sodium or potassium cyanide.
The amines released in accordance with the above reaction scheme can, if they are volatile under the implementation conditions, collect in dilute acid, otherwise they are obtained, for. B. back by fractional distillation of the reaction mixture.
The 2- (cyanomethyl-) cyclooctanone- (1) obtained is a water-insoluble, colorless liquid with a slight smell of bitter almonds, which can be purified by distillation. It shows the properties typical of a γ-ketonitrile.
The saponification of this nitrile is expediently effected by heating with aqueous alkali lye. The 1-ketocyclooctyl-2-acetic acid can be obtained from the solution of its alkali salt obtained by neutralizing it, e.g. B. with salts of sulfuric acid win.
The new γ-keto acid obtained in this way and its water-soluble salts have a cholagogue effect which, in experiments on guinea pigs, has been found to be considerably greater than that of dehydrocholic acid.
The parts mentioned in the examples are parts by weight.
example 1
146 parts of 2-dimethylaminomethylcyclooctanone (1) iodomethylate (melting point 182-184 "C, prepared by reacting 91 parts of 2-dimethylaminomethylcyclooctanone- (1) with 106 parts of methyl iodide in ethyl acetate) are dissolved in a solution of 66 parts of sodium cyanide in 1320 parts The initially clear solution is heated to 65 to 700 ° C. for about 100 minutes, trimethylamine escaping and the 2-cyanomethylcyclooctanone (1) separating out as an oil, then allowed to cool, the oil is separated off and the aqueous solution is extracted Layer with ether, combine the ether extract with the oil, dry with sodium sulfate and evaporate the ether.
The residue yields 68 parts of 2-cyanomethylcyclooctanone- (1) from Kr ,, = 106 to 1070 C. The ketonitrile can be characterized by its semicarbazone, which melts at 127 to 128 C.
68 parts of 2-cyanomethylcyclooctanone- (1) are refluxed with a solution of 115 parts of potassium hydroxide in 460 parts of water for 7 to 8 hours. After cooling, the saponified portions are removed by extraction with ether, whereupon the aqueous-alkaline layer is mixed with hydrochloric acid until the Congo acidic reaction occurs. The free 1-ketocyclooctyl-2-acetic acid is generally initially separated as oil. The aqueous layer is extracted with ether, the ether extract is combined with the oil, dried over sodium sulfate and the ether is evaporated off. 67 parts of 1-keto-cyclooctyl-2-acetic acid are obtained which, after recrystallization from cyclohexane, melts at 71 to 720.degree.
Your phenylhydrazone has a melting point of 109 to 110 ° C. (with decomposition).
Example 2
97 parts of 2-trimethylammoniummethylcycloctanon- (l) -methyl sulfate (melting point 99 ° C., prepared by reacting 73 parts of 2-dimethylaminomethylcyclooctanone- (1) with 252 parts of dimethyl sulfate in dry tetrahydrofuran with the addition of small amounts of glacial acetic acid at 10-15 ° C. ) are reacted with the solution of 48 parts of sodium cyanide in 950 parts of water as in Example 1. 36 parts of 2-cyanomethylcyclooctanone- (1) and 36 parts of 1-ketocyclooctyl-2-acetic acid are obtained.
Example 3
44 parts of 2-dimethylaminomethylcyclooctanone (1) hydrochloride (melting point 138-139 "C with decomposition, prepared by introducing dry hydrogen chloride into a solution of 40 parts of 2-dimethylaminomethylcyclooctanone (1) in 160 parts of absolute ethanol with cooling and precipitation with absolute ether) are reacted with a solution of 30 parts of sodium cyanide in 600 parts of water as in Example 1. After saponification of the nitrile, 18 parts of 1-ketocyclooctyl-2-acetic acid are obtained.
Example 4
108 parts of 2-piperidinomethylcyclooctanon- (1) iodomethylate (melting point 126-128 "C, prepared by heating a solution of 87 parts of 2-piperidinomethylcyclooctanone- (1) in 160 parts of absolute ethanol with 82 parts of methyl iodide and precipitation with absolute ether) reacted with a solution of 45 parts of sodium cyanide in 900 parts of water as in Example 1. After saponification of the nitrile, 30 parts of 1-ketocyclooctyl-2-acetic acid are obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE345885X | 1955-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH345885A true CH345885A (en) | 1960-04-30 |
Family
ID=6254881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH345885D CH345885A (en) | 1955-09-28 | 1956-08-20 | Process for the preparation of 1-ketocyclooctyl-2-acetic acid |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH345885A (en) |
-
1956
- 1956-08-20 CH CH345885D patent/CH345885A/en unknown
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