Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-01-11
2000-02-01
Owens, Amelia
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549358, 549359, 549366, 549374, C07D31914, C07D31906, C07D30900
Patent
active
060205032
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for preparation of a 1,4-benzodioxane derivative useful for an intermediate of circulatory drugs and drugs for psychoneurosis which are .alpha. and .beta.-adrenergic antagonists.
BACKGROUND ART
A 1,4-benzodioxane derivative is used for an intermediate for preparation of circulatory drugs and drugs for psychoneurosis which are .alpha.- and .beta.-adrenergic antagonist-activity and its various kind of processes are known. For example, the method by reacting a catechol derivative with glycidyl tosylate in the presence of sodium hydride (Japanese patent publication No.6-9613(1994)) or the method by reacting a catechol derivative with epichlorohydrin in the presence of pyridine (J. Org. Chem. 46,3846(1981)) is known. A method is also known to make a 1,4-benzodioxane skeleton by reacting a catechol derivative with glycerol 1-tosylate acetonide and, after removing the protective group, the acetonide, by introducing two tosyl group onto it and then by isolating it, and further by cyclizing it (J. Chem. Soc., Chem. Commun., 921(1976)).
DISCLOSURE OF INVENTION
Among the above known methods, besides the method comprising use of glycidyl tosylate is costly because of expense of its compound, the epoxy group is also reduced on the deprotection by hydrogenolysis and the yield decreases. In the method comprising the use of epichlorohydrin, the excess of epichlorohydrin and dichloropropanediol as a by-product must be eliminated by their evaporation with xylene, and the hydrochloric acid and acetic acid used must be eliminated by evaporation with ethanol and therefore, such procedures are troublesome. Moreover, the reaction is carried out under reflux of piperidine or hydrochloric acid. Accordingly, a compound with substituents which are unstable to an acid or a base can not be used. When using an optically active epichlorohydrin, racemization occurs and an optically pure product cannot be obtained. In the method comprising the reaction of a catechol derivative with glycerol 1-tosylate acetonide, the resulting ditosylated product must be separated after tosylation and therefore, yield of the ditosylated product is 55% or lower. These methods have many disadvantages in application of an industrial scale. An improved method has been desired.
The present inventors, taking into the consideration of the above fact, extensively engaged in study to find an improved method for preparation of a 1,4-benzodioxane derivative. As a result it was found that after carbonating a phenoxypropanediol compound, by cyclizing the resulting product by heating or by treating with a base, the desired 1,4-benzodioxane derivative is favourably obtained in an industrial scale.
The present invention relates to a process for preparation of a 1,4-benzodioxane derivative shown by the following formula (1), which is characterized in reacting a diol compound as shown by the following formula (2) with a carbonating agent to prepare a carbonate compound shown by the following formula (3), removing a protective group of the carbonate compound to prepare a phenol derivative shown by the following formula (4), and then cyclizing the phenol derivative by heat-treatment or by treatment with a base or a fluoride salt. ##STR2##
In the above formulae (1)-(4), R.sup.1 is a protective group of hydroxy, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and hydrogen, halogen, hydroxy, nitro, cyano, formyl, hydroxycarbonyl, alkoxycarbonyloxy in which the alkyl portion has 1-4 carbon atoms, alkyl having 1-4 carbon atoms, alkoxy having 1-4 carbon atoms, haloalkyl having 1-4 carbon atoms, N,N-dialkylamino in which the alkyl has 1-4 carbon atoms, alkylcarbonyl in which the alkyl portion has 1-4 carbon atoms, alkoxycarbonyl in which the alkyl portion has 1-4 carbon atoms, or phenyl which may be substituted by one or more alkyls having 1-4 carbon atoms, and adjacent two groups of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 may constitute a methylenedioxy, or may constitute a benzene ring via carbon atoms
REFERENCES:
II Farmaco Scientific Edition, vol. XLIII, Supp. To No. 12, Dec. 1988, "Dedicated to III Meeting Heterocyclic Structures in the Medicinal Chemistry Research", May 1988.
Nelson et al., J.C.S. Chem. Comm., "Absolute Configuration of 2-Alkylaminomethylbenzodioxans, Competitive .alpha.-Adrenergic Antagonists", 1976.
Willard et al., J. Org. Chem., "Potential Diuretic-.beta.-Adrenergic Blocking Agents: Synthesis of 3-[2-[(1,1-Dimethylethyl)amino]-1-hydroxyethyl]-1,4-dioxino[2,3-g]quinolin es", 1981, 46, 3846-3852.
Furukawa Yoshiro
Kitaori Kazuhiro
Matsui Shouhei
Daiso Co. Ltd.
Owens Amelia
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