Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1991-11-06
1993-05-25
Shaver, Paul F.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
564183, 564189, 564221, C07C10160
Patent
active
052142027
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to a method for preparing a compound having a retinoid activity, which is favorable for the production of such a compound on an industrial scale. It also relates to a novel crystal form of 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid which is useful as a medicament, and a method for preparation thereof.
BACKGROUND OF THE INVENTION
The compound obtained by this invention has been prepared by allowing tetrahydronaphthylamine derivative to react with monoester terephthalic halide and then subjecting to de-esterification (JP. Unexamd Pat. Publn. No. 61-76440). This method is, however, unfavorable for the production of the objective compound on an industrial scale, because starting amine derivative is not readily available, this amine derivative is toxic to the human body and more complicated steps are required. Moreover, it may be difficult in some cases to say that the obtained compound by this method is suitable for formulation.
DISCLOSURE OF THE INVENTION
This invention provides a method for preparing the objective compound advantageously in a simple procedure, with high purity and yield from a starting material which is readily available on an industrial scale, inexpensive, and not harmful to the human body.
The present invention provides a process for the preparation of the objective compound (V): ##STR2## wherein R.sup.2, R.sup.7 and R.sup.9 are independently hydrogen or lower alkyl, and R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently lower alkyl, which comprises:
(a) subjecting acyl aniline derivative (I): ##STR3## wherein R.sup.1 is lower alkyl or aryl and R.sup.2 is the same as above, and 1,4-butyl dihalide derivative (II): ##STR4## wherein R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are respectively the same as above, and X is halogen, to Friedel-Crafts reaction in an inert solvent in the presence of a Friedel-Crafts catalyst, thereby obtaining a novel bicyclic amide compound of the general formula (III): ##STR5## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are respectively the same as above;
(b) reacting the thus obtained bicyclic amide compound with a halogenating agent and an alcohol in sequence, and then subjecting to acyl exchange reaction with monoester terephthalic halide, thereby obtaining an amide compound of the general formula (IV): ##STR6## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.9 are respectively the same as above, and R.sup.8 is lower alkyl; and
(c) hydrolizing this compound.
In this invention, the term "lower alkyl" refers to an alkyl group of 1 to 4 carbon atoms, examples of which are methyl, ethyl, i-propyl, butyl, i-butyl, t-butyl and the like.
The term "aryl" refers to a phenyl group, a substituted phenyl group or the like. The substituent replacing the hydrogen of a phenyl ring can be any one of those which are inactive to the reaction, examples of which are lower alkyl, lower alkoxy carbonyl, nitro, halogen and the like.
As the Friedel-Crafts catalyst used in the step (a), conventional catalysts for Friedel-Crafts reaction can be used, such as Lewis acids (e.g., AlCl.sub.3, AlBr.sub.3, ZnCl.sub.2, ZnCl.sub.4, ZnBr.sub.2, ZnBr.sub.4, BF.sub.3 and a solvation thereof with an ether, SnCl.sub.4, SnBr.sub.4, TiCl.sub.4 and TiBr.sub.4), protoic acids (e.g., sulfuric acid, anhydrous hydrofluoric acid, phosphoric acid, polyphosphoric acid, perchloric acid, chlorosulfonic acid, fluorosulfonic acid, organic sulfonic acids, trifluoroacetic acid, chloroacetic acid, and the like), and cation-exchange resins, metal-cation forming agent (e.g., AgClO.sub.4, AgBF.sub.4, AgPO.sub.4, AgSbF.sub.6, AgPF.sub.6, and AgAsF.sub.6). Particularly preferred are Lewis acids. The molar amount of catalysts to be used is 0.5- to 5-times, preferably 1- to 3-times, and more preferably 1.5- to 2-times the molar amount of acylated aniline to be used as a starting material.
Although acylated aniline may be used in a molar amount equivalent to that of butyl diha
REFERENCES:
patent: 4221814 (1980-09-01), Takaku et al.
patent: 4221815 (1980-09-01), Weyer et al.
patent: 4227014 (1980-10-01), Shepherd
patent: 4989090 (1989-12-01), De Vries et al.
Hamada Yoshinori
Sakata Teruo
Uenaka Masaaki
Yamada Isamu
Shaver Paul F.
Shionogi & Co. Ltd.
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