• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Invention relates to improved processes for preparing 5-fluoro-2-methyl-1-(p-methylsulfinylbenzylidene)-indenyl-3-acetic acid, to intermediates thereof, and to the preparation of said intermediates.
    公开号:SU860695A1
    申请号:SU752175253
    申请日:1975-09-24
    公开日:1981-08-30
    发明作者:Джеймс Тулл Роджер；Грегори Мелилло Дэвид
    申请人:Мерк Энд Ко (Фирма)；
    IPC主号:
    专利说明:

    bridges from the nature of the restorer. The preferred reducing agent is sodium borohydride in water, which is pre-alkalized. The reducing agent is used in a concentration of 0.25-3 mol per 1 mol of indanone, preferably 1.2-2 mol. The reaction can be carried out at 0 ° C-85 ° C, preferably 4082 0. Hydrogenation of 5-fluoro-2-methylindanone-3-acetic acid can also be carried out by catalytic hydrogenation, which is carried out using a suitable hydrogenation catalyst, such as nickel, iridium, rhenium, ruthenium, rhodium, platinum or palladium, or reduced oxides metals, at pressures from atmospheric to 200 atm, preferably from atmospheric to 10 atm. The concentration of the catalyst is from 0.1 to 10 wt.% based on the weight of indanone, preferably from 1 to 5%. Suitable solvents for this reaction are saturated hydrocarbons, alcohols, ethers and water, or mixtures thereof, for example hexane, methanol, ethyl alcohol, ethyl acetate and water. The catalysts can be applied to a charcoal type carrier. 5-Fluoro-2-methylindanol-3-acetic acid is dehydrated under acidic or alkaline conditions, preferably under alkaline conditions, by heating 5-fluoro-2-methylind-1-ene-3-acetic acid. Both organic and inorganic acids can be used, preferably mineral acids, alkylsulfonic acids and arylsulfonic acids, such as p-toluenesulfonic acid, hydrochloric acid, sulfuric acid and methanesulfonic acid. The acid concentration is from 0.001 to 10 mol / mol of indanol, preferably from 0.01 to 0.2 mol. Acid dehydration can be carried out in an inert organic solvent, such as hydrocarbons or halogenated hydrocarbons, or mixtures thereof. Preferred solvents are ethylbenzene, toluene xylene and benzene. Dehydration can also be carried out under alkaline conditions. Suitable bases include sodium alkoxides, sodium amide, potassium alkoxides, alkali metal hydroxide and alkaline earth metal hydroxide. The main dehydration is carried out in an inert organic solvent, such as alcohols, ethers, and mixtures thereof. Suitable solvents are glyme, di glyme, triglyme, methanol, ethyl, isopropyl alcohol and tertiary butyl alcohol, and preferred are ethyl and isopropyl alcohol. Dehydration can be carried out at 20-150 s, preferably 60-100 ° C. Dehydration in an acidic medium results in iid-1-ene, while dehydration in an alkaline medium leads to ind-2-ene. The introduction of the benzylidene substance: -, - the body into the indenic acid compound is carried out by reaction with p-methylsulfinyl (or p-methylthio) benzaldehyme, in the presence of a strong base, at temperatures from 0 to, preferably at 20-80 ° C, in an environment of solvent . Such strong bases as alkali metal and alkaline earth metal hydroxides, or the corresponding alcohols, tetra-C -Cb-alkylammonium hydroxides or benzyltri-C -C5 -alkylammo1 and, for example, benzyltrimethylammonium hydroxide and alkali metal hydrides are used. Suitable solvents are polar solvents, such as dimethoxyethane, methanol, pyridine, dimethylformamide, and nonpolar solvents, such as benzene, toluene, xylene. The resulting benzylidene-denenacetic acid salt is converted to the free acid in the presence of strong organic acids (p-toluenesulfonic acid, trifluoroacetic acid) or mineral acids (hydrochloric, sulfuric). If p-methylthiobenzaldehyde is used in condensation, the oxidation of methylthio groups to the methylsulfinyl group is carried out, for example, by oxidation of HgO, periodates and alkaline and alkaline earth metals, or organic peracids, such as peracetic acid and monoperphthalic acid. The reaction is preferably carried out in the presence of a solvent, such as C-Su-alkanoic acids (acetic acid), halogenated hydrocarbons (chloroform, 1,2-dichloroethane), esters (dioxane) of C-C5 alkanols (isopropyl alcohol) or their mixes. The above reactions can be carried out without scavenging the products in a single reactor. Example 1. 5-Fluoro-2-methylindanol-3-acetic acid. To a solution of 390 mg (1.8 mmol) of 5-fluoro-2-m thilendanone-73-acetic acid in b ml of isopropyl alcohol was added 2.5 M sodium hydroxide solution to a pH value. To this solution was added 100 mg of borohydride (2.6 mmol}). The solution was stirred at room temperature for 80 minutes and for 45 minutes. The solution was poured out into 2 M molar acid and extracted with methylene chloride. The organic layer was dried and concentrated. Example 2. 5 Fluoro-2-methylindanol-3-acetic acid.
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining 5-fluoro-2-methyl-1- (n-methylsulfinyl benzylidene) -indenyl-3-acetic acid of the Formula (I) characterized in that, in order to simplify the process, 5-fluoro-2-methylindanone-3-acetic acid restore in 5-fluoro-2-methylindanol-3-acetic acid, which is subjected to dehydration, and the resulting 5-fluoro-2-methylinden-3-acetic acid of the formula (II)
    CHjCOOH
    CH 3 is condensed with p-methylsulfinylbenzaldehyde in the presence of a strong base in an organic solvent at a temperature of 0-100 ° C.
    类似技术:
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    同族专利:
    公开号 | 公开日
    NO146198C|1982-08-18|
    SE7510329L|1976-04-05|
    BE834080A|1976-04-01|
    DD125639A5|1977-05-04|
    FI61690B|1982-05-31|
    YU141481A|1982-02-28|
    HU171805B|1978-03-28|
    FI61690C|1982-09-10|
    ATA734575A|1977-11-15|
    LU73496A1|1976-08-19|
    CH615158A5|1980-01-15|
    FI752573A|1976-04-03|
    NO753179L|1976-04-05|
    JPS51105049A|1976-09-17|
    YU239875A|1982-06-30|
    NL7510944A|1976-04-06|
    NO791267L|1976-04-05|
    PL103093B1|1979-05-31|
    US3998875A|1976-12-21|
    NO141050C|1980-01-02|
    NO146198B|1982-05-10|
    NO141050B|1979-09-24|
    CS183821B2|1978-07-31|
    AT344154B|1978-07-10|
    GB1483980A|1977-08-24|
    FR2286817B1|1979-01-05|
    DK416975A|1976-04-03|
    FR2286817A1|1976-04-30|
    SU995705A3|1983-02-07|
    PL103733B1|1979-07-31|
    ES441404A1|1977-03-01|
    US4123457A|1978-10-31|
    SU957760A3|1982-09-07|
    DE2543870A1|1976-04-22|
    CS183850B2|1978-07-31|
    引用文献:
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    US3532752A|1965-12-30|1970-10-06|Merck & Co Inc|1-alkylidene-3-indenyl aliphatic amines|
    US3547923A|1968-03-25|1970-12-15|Bristol Myers Co|Piperazyl ethyl 7h-benzocycloheptenes|
    US3725548A|1970-05-01|1973-04-03|Merck & Co Inc|Substituted indenyl acetic acids in the treatment of pain, fever or inflammation|
    US3692825A|1970-05-01|1972-09-19|Merck & Co Inc|Indanyl acetic acids|
    US3766259A|1970-05-01|1973-10-16|Merck & Co Inc|Preparation of 1-aryl-3-indenyl acetic acids|
    US3654349A|1970-05-01|1972-04-04|Merck & Co Inc|Substituted indenyl acetic acids|
    US3870753A|1973-12-20|1975-03-11|Merck & Co Inc|Process for preparing indenyl acetic acids|US4368127A|1979-07-02|1983-01-11|Akzona Incorporated|Fabric softening compounds and method|
    DE3266350D1|1981-06-11|1985-10-24|Sumitomo Chemical Co|Tetrahydronaphthalene derivatives and their production|
    IT1190371B|1985-06-19|1988-02-16|Zambon Spa|PROCESS FOR THE PREPARATION OF CIS-5-FLUORO-2-METHYL-1--INDENYL-3-ACETIC ACID|
    US6063818A|1996-06-13|2000-05-16|Cell Pathways Inc.|Substituted benzylidene indenyl formamides, acetamides and propionamides|
    US5998477A|1996-06-13|1999-12-07|Cell Pathways Inc.|Substituted methoxy benzylidene indenyl-acetic and propionic acids for treating patients with precancerous lesions|
    US5965619A|1996-06-13|1999-10-12|Cell Pathways Inc.|Method for treating patients having precancerous lesions with substituted indene derivatives|
    US6121321A|1996-06-13|2000-09-19|Cell Pathways, Inc.|Substituted methoxy benzylidene indenyl acetic and propionic acids for treating patients with precancerous lesions|
    CA2261193C|1996-07-01|2005-01-11|The Procter & Gamble Company|Dehydrated potato flakes|
    US5948779A|1997-12-12|1999-09-07|Cell Pathways, Inc.|Substituted condensation products of n-benzyl-3-indenyl acetamides with heterocyclic aldehydes|
    US6028116A|1998-04-03|2000-02-22|Cell Pathways, Inc.|Substituted condensation products of 1H-indenyl-hydroxyalkanes with aldehydes for neoplasia|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US05/511,349|US3998875A|1974-10-02|1974-10-02|Process of preparing 5-fluoro-2-methyl-1--indenyl-3-acetic acid|
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