Method of preparing substituted indanylcateic acid

专利摘要:
1484088 Alkyl indans SANDOZ Ltd 24 Oct 1974 [30 Oct 1973] 46116/74 Heading C5E [Also in Division C2] Compounds of formula wherein R 1 is C 1-4 alkyl, R 2 is H or C 1-4 alkyl, and either R 5 is C 1-4 alkyl and R 6 , R 7 are each H, or R 5 is H and R 6 , R 7 are each H or C 1-4 alkyl, are prepared by reducing the corresponding indan-1-ones. Many examples are given.
公开号:SU843732A3
申请号:SU752197008
申请日:1975-12-10
公开日:1981-06-30
发明作者:Глин Пэйн Тревор
申请人:Эксашими С.А. (Фирма)；
IPC主号:

专利说明:

(54) METHOD FOR OBTAINING A SUBSTITUTED INDANINO ACETIC ACID
one
The invention relates to a process for the preparation of indanyl acetic acid derivatives of the general formula
f
CH-COOH (T)
where r
lower alkyl
hydrogen or lower alkyl;
k
 hydrogen or lower alkyl;
R |
hydrogen, chlorine or lower alkyl; and if. R is hydrogen,
then Rg and RJ, mean hydrogen, chlorine
or lower alkyl,,
These can be used as physiologically active compounds.
The reaction of hydrolysis of ester or nitrile 1 is known.
The purpose of the invention is the production of indanilacetic acid-derived prodrugs, which allow the range of 4 iiologically active compounds to be expanded.
The goal is achieved by the fact that in the method of obtaining a substituted
indanyl acetic acid of general formula (I) ester or nitrile of general formula
BUT
CH-R7 (P)
ten
where R has the above values}
The R-, -CN or COORg group in which Rg is lower alkyl is subjected to alkaline or acid hydrolysis in the presence of an inert water-immiscible organic solvent when heated to boiling with subsequent extraction of the desired product.
Example 1. 2-Ethyl-5-indanacetonitrile is dissolved in 350 ml of ethane, a solution of 26.7 g of potassium hydroxide in 45 ml of water is added and the mixture is boiled under reflux for 20 hours. The solution is concentrated to 50 ml, diluted with water and extracted with ether, and the ether phase is discarded. The aqueous phase is then acidified with 2N. hydrochloric acid and extracted with ether.
The crude 2-ethyl-5-indan acetic acid obtained after condensing the ether extract was purified by chromatography on 50 times the amount of silica gel using chloroform, which contains 1.5% methanol, as a solvent. After recrystallization from hexane, the yield of the desired product is 70%, m.p. 44-46 ° Analogously to Example 1, the opsic derivatives in Example 2-10 are obtained. Derivatives of 5-indan-acetic acid from the corresponding derivatives of 5-indanacetoniril.
Example 2. 2-Isopropyl-about-methyl-5-indan acetic acid.
The resulting 2-isopropyl-a-methyl | -5-indan acetic acid is purified by chromatography on silica gel and recrystallized from hexane. T, pl 83-86.I
The resulting reaction with 2-amino-2-hydroxy-methyl-1, 3-propanediol (1,3-dioxy-2-hydroxymethyl-2-propyl) ammonium salt of 2-isopropyl-cx-methyl-5-indan acetic acid is crystallized from methanol (simple ether). T. pl. 14-0-141 ° C.
Example 3. 2-ETIH-2,6-dimethyl-5-indanacetic acid.
The resulting 2-ETHYL-2,6-dimethyl-5-indan acetic acid is recrystallized from petroleum ether at mp. 40-42 ° C. The melting point of the ammonium salt of cyclohexyl of the desired product is 15415 oC.
Example 4. 2-Isopropyl-5 -indane-acetic acid.
T. pl. 83-86C.
Example 5. 2-Ethyl-b-methyl-5-indan-acetic acid.
T. pl. 103-104s.
Example 6. 2-Ethyl-b-chloro-ot-methyl-5-indan acetic acid.
T. pl. 113-1150С.
Example 7. b-Chloro-2,2-dimethyl-5-indan acetic acid.
T. pl. 143-145 ° C.
Example 8. 2-Ethyl-6-chloro-2-methyl-5-indan-acetic acid.
T. pl. 87-89 “C.
Example 9. 2-Ethyl, 7-dimethyl-5-indan acetic acid.
T. pl, 103-105С.
Example 10. 2-ETHYL-4, 7-0 -trimethyl-5-indan acetic acid (based on 2-ethyl-4,7-dichloro-c-hydroxy-cX-methyl-5-indan acetic acid) .Т. square 98-1000s
Example 11. 2-Ethyl-6-chloro-2-methyl-α-indan-acetic acid.
A solution of 20 g of potassium hydroxide in 40 ml of water is added to a solution of 11.5 g of methyl 2-ethyl-6-chloro-2-methi-5-indanoacetic acid ester in 250 ml of methanol and refluxed for 1 h. . The cooled solution is concentrated, diluted with vrdoy
and the neutral components are extracted with ether. The aqueous phase is acidified with hydrochloric acid, extracted with ether, the ether extract is washed with water, dried over sodium sulfate and evaporated. The remaining 2-ethyl-b-chloro-2-methyl-5-indan acetic acid is recrystallized from hexane. T. pl. 87-89C, yield 85%.
Example 12. 2-Ethyl-5-indan acetic acid.
Get similar. Example 11. So pl. 44-4bps
The original products can be obtained as follows.
5 .Solution of 12.0 g of purified
2-ethyl-5-indanacetonitrile in 200 ml of ethanol is saturated under ice-cooling with gaseous hydrogen chloride. Then the solution is boiled for 20 hours with
0 phlegm, evaporated and redissolved in 170 ml of ethanol. Then 4.7 ml of water are added and the solution is boiled under reflux for 3 hours, evaporated and the residue is distributed between benzene and water.
The benzene phase is washed with a 5% sodium bicarbonate solution and water, dried and evaporated. The remaining oily residue 2-ethyl-5-indan acetic acid ethyl ester is distilled in a spherical expansion tube. Example 13. 2.2, sb-trimethyl-α-indanacetic acid.
17 g of methyl ester, 2,2, Qi-trimethyl-5-indan acetic
Acidic acid 5 was poured onto 8.2 g of potassium hydroxide in 160 ml of methanol and 16 ml of water in the same manner as in Example 11. After treatment of the reaction mixture, oily 2.2.0-trimethyl-5-in-0-dan acetic acid was obtained. The melting point of the ammonium salt of cyclohexyl of the desired product is 1801830 ° C (from ethanol).
5 Example 14. 2-Isopropyl-cc-methyl-5-indan-acetic acid-.
2-Isopropyl-c) C-methyl-5-and -do-acetic acid is obtained by reduction of 5-indan-acetic acid of complex methyl ester with -oxy-2-isopropyl-c-methyl and is processed further without purification. T. pl. 83-8bs.
Example 15. A solution of 1250 g of 2-methyl (2-ethyl) -5-indanyl-aceto. nitrile in 2 liters of acetic acid,
2 liters of sulfuric acid and 2 liters of water are brought to reflux for 20 hours. It is then cooled, combined with water and ice, and extracted with ether. The ether phase is extracted several times with a solution of ammonium hydroxide. The ammonium hydroxide phase is acidified and the acid is extracted with petroleum ether, which is washed with water and dried. Get 1264 g

权利要求:
Claims (1)
[1]
5 2-methyl (2-ethyl) -5-indanyl acetic acid in the form of white crystals with so pl. 47-480C. Yield 92%. Example 16. A solution of 798 g of 2-methyl- (2-isopropyl) -5-indanyl acetonitrile in 2 liters of acetic acid, 1 liter of sulfuric acid and 1 liter of water is brought to reflux for 20 hours. Then it is cooled, combined with water and ice and extracted with ether. The ether phase is washed 2 times. water is then extracted several times with a solution of ammonium hydroxide. The ammonium hydroxide phase is acidified cold with normal hydrochloric acid and the acid is extracted with petroleum ether, which is washed with water and dried. 722.5 g of 2-methyl- (2-isopropyl) -5-indanyl acetic acid are obtained in the form of white crystals with m, pl. 86-88c. Yield 83%. Claims of Invention A method of producing a substituted indanyl acetic acid of the general formula 1, wherein R is lower alkyl; R, j is hydrogen or lower alkyl; RO is hydrogen or lower alkyl; Rjj is hydrogen, chlorine or lower alkyl and if Rj is hydrogen, then Rg and R are hydrogen, chlorine or lower alkyl, characterized in that the ester or nitrile of the general formula fL CH-R, where R, is Rjj, is as defined above The R, - CN or COORo group, in which Rg is lower alkyl, is subjected to alkaline or acid hydrolysis in the presence of an inert organic water-immiscible solvent when heated to boiling, followed by release of the desired product. Sources of information taken into account during the examination 1. Buhler K., Pearson D. Organic syntheses. M., Mir, 1973, Part 2, p. 223-228.

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---

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---

DE2546906A1|1974-10-29|1976-09-30|Sandoz Ag|NEW ARYL ACID ACIDS THEIR PRODUCTION AND USE IN MEDICINAL PRODUCTS|

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FR2379511A1|1977-02-02|1978-09-01|Hexachimie|Analgesic and antiinflammatory lysine salt - of alpha-methyl-2-isopropyl-5-indanyl-acetic acid|

---

LU77254A1|1977-05-04|1979-01-18|

---

JPH0118141Y2|1984-02-03|1989-05-26|

---

US5179229A|1992-04-24|1993-01-12|Hoechst Celanese Corporation|Preparation of 2,2-diorgano-3-arylpropionic acids and esters thereof|

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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CH1525173A|CH592598A5|1973-10-30|1973-10-30|

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