Process for preparation of glycidyl ether

Details Process for preparation of glycidyl ether Process for preparation of glycidyl ether

1990-08-22

1994-10-25

Ivy, C. Warren

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549517, C07D31104

Patent

active

053590970

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to a new process for preparation of glycidyl ethers useful as an intermediate for preparation of chemical drugs such as medicines or agricultural chemicals, particularly medicines having a .beta.-adrenoreceptor blocking action or the like.


BACKGROUND OF THE INVENTION

.beta.-adrenoreceptor blocking agents have been widely used for curing or treatment of circulatory system diseases such as hypertension, angina pectoris and arrhythmia, and many of them are aryloxypropanolamines having a structure represented by the following formula ##STR2## wherein Ar represents a mother nucleus such as an aryl group and R represents a lower alkyl group or the like.
Various processes for preparation of a compound represented by the above formula (1) have been reported, and a typical one among them is a process shown by the following reaction formula ##STR3##
That is, the typical process is a process which comprises making an epoxy compound (3) act on an aryl alcohol (2) to prepare a glycidyl ether (4), and then making an amine (5) act thereon to prepare a desired aryloxypropanolamine (1).
In the above reactions, the reaction of the glycidyl ether (4) with the amine (5) as the second reaction generally proceeds with a good yield without occurrence of side reactions and thus there is no particular problem about the reaction, whereas the reaction of the aryl alcohol (2) with the epoxy compound (3) as the first reaction has, particularly in preparation of an optically active product, problems of lowering of optical purity and the like. ##STR4## [Please refer to Japanese Patent Publication No. 54317/1986; Japanese Laid-Open Patent Publication No. 167981/1982; J. Med. Chem., 15(3), 260-266(1972); etc.] ##STR5## Please refer to J. Am. Chem. Soc., 101, 3666(1979); Chem. Pharm. Bull., 35(9), 3691-3698(1987); etc.] ##STR6## Please refer to Japanese Laid-Open Patent Publication No. 208973/1985; Chem. Pharm. Bull., 35(9), 3691-3698(1987)] ##STR7## [Please refer to WO190/1988] ##STR8## [Please refer to J. Med. Chem., 15(3), 260-266(1972); and J. Med. Chem., 23(10), 1122-1126(1980)]
Among these processes, the processes of the above (1) and (2) are processes wherein heating is carried out in the presence of a base such as sodium hydroxide or potassium carbonate, and thus are not suitable in case an aryl alcohol as a raw material is unstable against the base. For example, in case the raw material is an aryl alcohol having on the mother nucleus (Ar) a nitroxy group, an acylamino group, an alkylaminocarbonylalkoxy group, an alkoxycarbonyl group or the like, there is a drawback that these groups are liable to be eliminated or hydrolyzed by the base. Further, there is another drawback that when these processes are applied to preparation of an optically active product, optical purity of the resulting glycidyl ether is lowered.
On the other hand, in the process of the above (3), lowering of optical purity occurs only to a small extent, but it is necessary to prepare as a raw material an optically active glycidyl sulfonate and thus the process is industrially disadvantageous.
Further, the process of the above (4) has a drawback of low yield and formation of several by-products which are hard to remove.


SUMMARY OF THE INVENTION

The object of this invention is to provide a novel process for preparation of a glycidyl ether which does not have the drawbacks as above-mentioned, brings about only a small lowering of optical purity even when it is applied to preparation of an optically active product, and is capable of preparing the glycidyl ether industrially advantageously and in a high yield.
According to this invention, a process is provided for preparation of a glycidyl ether represented by the general formula ##STR9## wherein A represents an aryl group optionally having a substituent(s) or a heteroaryl group optionally having a substituent(s), and the carbon atom marked with * is an asymmetric carbon, if necessary, further treating the reaction product with a base.


DETAILED DESCRIPTION OF THE INVENTIO

REFERENCES:
patent: 4582892 (1986-04-01), Chang et al.
patent: 4677170 (1987-06-01), Monnier et al.
Chemical Abstracts, vol. 110, No. 9, Feb. 27, 1989, p. 507, Abstract No. 73883q.

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