Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-04-29
2000-07-11
Trinh, Ba K.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549516, C07D30128, C07D30323
Patent
active
060875127
DESCRIPTION:
BRIEF SUMMARY
1. TECHNICAL FIELD
The present invention relates to a process for preparation of glycidyl ethers and optical active compounds thereof important as intermediates for synthesis of medicines and physiologically active compounds.
2. BACKGROUND ART
Glycidyl ethers are important intermediates for synthesis of many kinds of medicines. For example, so called .beta.-receptor blocking agents which are often used as circulatory drugs, especially antihypertensive agents and antiarrhythmic agents, are basically prepared from glycidyl ethers.
The glycidyl ethers have been prepared by reacting a corresponding alcohol with an epoxy compound, such as epichlorohydrin or glycidyl p-toluenesulfonate. The reaction of the alcohol with epichlorohydrin or glycidyl p-toluenesulfonate is carried out in the presence of an alkali metal base, such as sodium hydride or sodium hydroxide, or an organic base, such as triethylamine or pyridine, or in the presence of catalyst, such as a mineral acid (e.g., sulfuric acid) or Lewis acid (e.g., tin tetrachloride) to prepare a 3-chloro or tosyloxy-2-propanol derivative and it was treated with a base to prepare a glycidyl ether. However, in case of carrying out in the base i n the former, the epoxy compound, such as epichlorohydrin or glycidyl p-toluenesulfonate must be used in excess and therefore, the reaction is not economical. In case of using a strong base, such as sodium hydride or sodium hydoxide, the after-treatment, such as neutralization is necessary and it is troublesome. In case of using sodium hydride there is a possibility of burning in the after-treatment. On the other hand, in case of the latter in acidic conditions the reaction steps are many and the treatment is troublesome. Furthermore, in case of using an aryl derivative having a substituent unstable in basic conditions, the yield is not good.
By the way, glycidyl ethers have an asymmetric carbon atom and exist in optical isomers. Recently in developing the medicines comprising optical isomers, each isomer is investigated. Therefore, it becomes very important to establish a method to prepare easily an optically active compound with highly optical purity of these compounds. In order to solve such problems, combinations of many kinds of bases with an optically active epichlorohydrin, glycidyl p-toluenesulfonate, or glycidyl m-nitrobenzenesulfonate have been investigated. These methods, for instance, are described in Japanese Patent Publication No. 1-121282, Japanese Patent Publication No. 1-279890, Japanese Patent Publication No. 1-279887, European Patent No. 454385, Japanese Patent Publication B No. 6-37449, Chem. Pharm. Bull., 35, 3691 (1987), Chem. Pharm. Bull., 38, 2092 (1990), J. Org. Chem., 54, 1295 (1989) and so on.
However, in all these methods, marked racemization occurs on the reaction and the optical purity decreases.
Optical purity of an glycidyl ether prepared by reacting p-hydroxyphenylacetoamide and an optically active epichlorohydrin in sodium hydroxide as a base decreases to 90% e.e. and it is not satisfactory.
The present inventors engaged extensively in solving above problems, and found to prepare easily and with good yield a glycidyl ether by reacting an epoxy compound and an alcohol in the presence of a fluoride salt. Furthermore, when an optically active epoxy compound is used, the object compound obtained is also optically active, and marked racemization does not occur on the reaction.
DISCLOSURE OF INVENTION
The present invention relates to a process for preparation of a glycidyl ether of the formula ##STR2## wherein R is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic ring, ##STR3## wherein X is halogen or sulfonyloxy group, with an alcohol of the formula
Examples of halogen shown by X in the formula (1) are chlorine atom, bromine atom and iodine atom, preferably chlorine atom and bromine atom. Examples of sulfonyloxy group shown by X in the formula (1) are preferably a substituted or unsubstituted alkylsulfonyloxy having 1 to 10 car
REFERENCES:
Shiratsuchi et al., Chem. Pharm Bull., "Synthesis and Activity of Optical Isomers of Nipradilol," 35 (9) 3691-3698 (1987).
Kawamura et al., Chem. Pharm. Bull., "An Efficient Synthesis of the Optical Isomers of Nipradilol," 38 (8) 2092-2096 (1990).
Klunder et al., J. Org. Chem., "Arenesulfonate Derivatives of Homochiral Glycidol: Versatile Chiral Building Blocks for Organic Synthesis," 54, 1295-1304 (1989).
Furukawa Yoshiro
Kitaori Kazuhiro
Mikami Masafumi
Otera Junzo
Yanagimoto Tetsuya
Daiso Co. Ltd.
Trinh Ba K.
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