Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Patent
1991-07-10
1992-08-25
Brust, Joseph Paul
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
558408, 560 35, 560 51, 560 53, C07C25537, C07C25540, C07C25562
Patent
active
051420910
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to .alpha.,.beta.-unsaturated ketone and ketoxime derivatives which are novel compounds. The present compounds are useful as intermediates for preparing (3,4-diarylisoxazol-5-yl)acetic acid derivatives which are represented by the formula ##STR2## wherein R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or lower alkoxyl, and which are useful as anti-inflammatory agents, analgesics and antipyretics.
BACKGROUND ART
JF-A-59764/1981 discloses (3,4-diarylisoxazol-5-yl)acetic acid derivatives as a compound having anti-inflammatory, analgesic and antipyretic activities. The processes thereof are known in (1) the above publication and (2) JP-A-75471/1985.
JP-A-59764/1981 ##STR3## wherein R.sup.1 and R.sup.2 are as defined above.
The above contemplated compound is obtained by reacting 3,4-diaryl-5-methylisoxazole with n-butyl lithium in tetrahydrofuran while cooling by use of dry ice-acetone mixture, pouring the reaction mixture into pulverized dry ice, and then treating the mixture with acid.
JP-A-75471/1985 ##STR4## wherein X is halogen atom, R.sup.1 and R.sup.2 are as defined above. This process comprises reacting 3,4-diaryl-5-methylisoxazole with a halogenating agent and then with a cyanogenation agent to obtain 3,4-diaryl-5-cyanomethylisoxazole, and subjecting the same to solvolysis.
The present inventors have investigated an industrial process for preparing (3,4-diarylisoxazol-5-yl)acetic acid derivatives and found the methods disclosed in (1) and (2) have various problems. In the method (1), the reagent, n-butyl lithium, is liable to ignite and causes problems in fire and safety when used in a large quantity. Further, this method comprises problems in process efficiency including operation efficiency, because dry ice having high hygroscopicity is used in the reaction which requires anhydrous reaction condition and low temperature -70.degree.C. The method (2) is more complicate than the method (1), and is not a preferable industrial process in view of safety due to the use of cyano compound.
An object of the present invention is to provide novel .alpha.,.beta.-unsaturated ketone and ketoxime derivatives useful as intermediates for preparing the compound (A) by a simple process which uses no dangerous reagent and is excellent in safety and operation efficiency.
DISCLOSURE OF THE INVENTION
The present invention provides an .alpha.,.beta.-unsaturated ketone and ketoxime derivative represented by the formula ##STR5## wherein Y is oxygen atom or hydroxyimino group, Z is cyano or alkoxycarbonyl group, R.sup.1 and R.sup.2 are the same or different and are each hydrogen atom or lower alkoxyl group.
In the present invention, examples of alkoxycarbonyl groups represented by Z are straight-chain or branched-chain alkoxycarbonyl groups having 2 to 7 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, secbutoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and hexyloxycarbonyl. Examples of lower alkoxyl groups represented by R.sup.1 and R.sup.2 are straight-chain or branched-chain lower alkoxyl groups having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, secbutoxy. tert-butoxy, pentyloxy and hexyloxy. The present .alpha.,.beta.-unsaturated ketone and ketoxime derivatives are useful as intermediates for preparing (3,4-diarylisoxazol-5-yl)acetic acid derivatives which are useful as anti-inflammatory agents, analgesics and antipyretics and which are represented by the formula ##STR6## wherein R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or lower alkoxyl group.
The compound (I) in the present invention is prepared, for example, in accordance with the following reaction scheme. ##STR7## wherein Z, R.sup.1 and R.sup.2 are as defined above, and R.sup.3 is lower alkyl group.
Examples of lower alkyl groups represented by R.sup.3 in the above scheme are straight-chain or branched-chain alkyl groups havi
REFERENCES:
C.A. Tanaka et al 115: 183271z (1991).
C.A. Tanaka et al 115: 158717t (1991).
C.A. Buggle et al 76: 59293v (1971).
C.A. Jan.-Jun. 1972-Formula Index, p. 1145f.
Hagiwara Yu-ichi
Kajitani Makoto
Tanaka Motoaki
Yasumoto Mitsugi
Brust Joseph Paul
Taiho Pharmaceutical Company Limited
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