Process for production of glycide derivative

Details Process for production of glycide derivative Process for production of glycide derivative

1994-01-13

1995-10-31

Ivy, C. Warren

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546141, 546290, 548484, 548136, 549466, 549475, 549462, C07D21520

Patent

active

054630614

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

This application is the national phase of PCT/JP93/00626, filed May 13, 1993.


TECHNICAL FIELD

The present invention relates to a process for producing a glycide derivative (an aryl glycidyl ether or heteroaryl glycidyl ether derivative) which is an important intermediate in production of drugs, particularly circulatory drugs, carcinostaticity-enhancing agents, etc. More particularly, the present invention relates to a process for producing a glycide derivative at a high efficiency and economically and, when the product is an optically active substance, at a high optical purity.


BACKGROUND ART

Glycide derivatives are important intermediates in production of various drugs. So-called .beta.-blockers, which are in wide use as, for example, circulatory drugs, particularly an antiarrhythmic drug and an antihypertensive drug, are produced basically using a glycide derivative as an important intermediate. The process for production of propranolol hydrochloride as an typical example of .beta.-blockers is shown below. Other .beta.-blockers are produced by similar reactions wherein other hydroxyaryl is used as a starting material in place of .alpha.-naphthol and a glycide derivative is used as an intermediate. ##STR2##
Quinoline derivatives used as a carcinostaticity-enhancing agent, etc., disclosed in Japanese Patent Application Kokai (Laid-Open) No. 101662/1991, etc. are produced by the following process using a glycide derivative as an intermediate. ##STR3##
As appreciated from these cases, glycides are important compounds in drug production. For production of glycides, there have conventionally been known, as shown previously, processes of reacting a corresponding hydroxyaryl with epichlorohydrin or glycidyl tosylate in the presence of a base of a metal such as sodium, potassium or the like or an organic base such as triethylamine, pyridine or the like. These processes, however, have had many problems in operation, safety, etc. in industrial large amount production and also problems in efficiency and economy.
Meanwhile, a series of these drugs each have an asymmetric carbon and are each an optically active substance. In recent years, in the development of drugs using optically active substances, the physiologically activities of each optically active substance have been investigated. In some cases, the optically active substance itself is used as a drug as in the case of, for example, penbutolol sulfate shown below. ##STR4##
Hence, it is an important task to establish processes for producing a series of the above products each in the form of an optically active substance easily and at a high optical purity (enantiomer excess % [% e.e.]). In order to achieve the task, it has hitherto been investigated to use optically active epichlorohydrin or optically active glycidyl tosylate in combination with various bases. Examples of such approaches are reported in Japanese Patent Application Kokai (Laid-Open) No. 121282/1989, Japanese Patent Application Kokai (Laid-Open) No. 279890/1989, Japanese Patent Application Kokai (Laid-Open) No. 279887/1989, European Patent 454385, Chem. Pharm. Bull., 35, 8691 (1987), Chem. Pharm. Bull., 38, 2092 (1990), J. Org. Chem., 54, 1295 (1989), etc. Of these processes, however, for example, when there are used sodium hydride as a metal base and dimethylformamide as a solvent and there are reacted 5-hydroxyquinoline and glycidyl tosylate, the resulting glycidyl ether has an optical purity of 80% e.e. or below, which is not satisfactory. That is, the above-mentioned optically active compounds have two reaction sites as shown below; their reactions are difficult to control; no process capable of producing an intended product at a satisfactory optical purity has been established yet. ##STR5##
Thus, there has been desired a novel process for producing a glycide derivative which is an important intermediate in drug production, efficiently and economically. There has also been strongly desired a process for producing said glycide derivative in the form of an optically active sub

REFERENCES:
patent: 5082847 (1992-01-01), Pascal
Klunder, "Arenesulfonate Derivatives of Homochiral Glycidol: Versatile Chiral Building Blocks for Organic Synthesis", J. Org. Chem., vol. 54 pp. 1295-1304, 1989.
Hackh's Chemical Dictionary, 3rd Edition, edited by Julian Grant, p. 31, 1944.

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