Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1999-04-28
2000-05-02
Barts, Samuel
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564349, 548503, C07C23300
Patent
active
060574763
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a process for preparation of 3-amino-2-hydroxy-l-propyl ethers useful for an intermediate for synthesis of .beta.-receptor blocking agents which are used as circulatory drugs, especially antihypertensive agents and antiarrhythmic agents.
BACKGROUND ART
The 3-amino-2-hydroxy-l-propyl ethers have been prepared by reacting a corresponding alcohol with an epoxy compound, such as epichlorohydrin or glycidyl p-toluenesulfonate to prepare a glycidyl aryl ether and reacting it with an amine. 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. However, in case of carrying out in the base, the epoxy compound, such as epichlorohydrin must be used in excess and therefore, the reaction is not economical. In case of using a strong base, such as sodium hydride, there is a possibility of burning in the post treating. Furthermore, in case of using an aryl derivative having a substituent unstable in basic conditions, the yield is not good.
By the way, 3-amino-2-hydroxy-1-propyl ethers have an asymmetric carbon atom and exist in optical isomers. Recently in developing 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, 8691 (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 3-amino-2-hydroxy-1-propyl ether prepared by reacting p-hydroxyphenylacetoamide and an optically active epichlorohydrin in sodium hydroxide as a base to prepare a glycidyl ether and then reacting it with diisopropylamine 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 an object compound of the formula (4) below by reacting an epoxy compound of the formula (1) below and an alcohol of (2) below in the presence of a fluoride salt and then, reacting it with an amine of the formula (3) below. Furthermore, when an optically active epoxy compound (1) is used, the object compound obtained is also optically active, and any marked racemization does not occur on the reaction. When an epoxy compound with highly optical purity is used, there is obtained an 3-amino-2-hydroxy-1-propyl ether with highly optical purity.
DISCLOSURE OF INVENTION
The present invention relates to a process for preparation of an 3-amino-2-hydroxy-l-propyl ether of the formula ##STR3## wherein R.sup.1 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic ring, R.sup.2 and R.sup.3 are the same or different hydrogen atom, substituted or unsubstituted alkyl, or may form a ring together with an adjacent nitrogen atom, which ring may be interrupted with a nitrogen atom, an oxygen atom or a sulfur atom, ##STR4## wherein X is halogen or sulfonyloxy group, with an alcohol of the formula 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 carbon atoms, such as methanesulfo
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
Yoshimoto Hiroshi
Barts Samuel
Daiso Co. Ltd.
LandOfFree
Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1595133