Organic compounds -- part of the class 532-570 series – Organic compounds – Silicon containing
Patent
1993-02-19
1994-10-11
Shaver, Paul F.
Organic compounds -- part of the class 532-570 series
Organic compounds
Silicon containing
556428, 556429, 556437, 549214, 558 44, 558 45, 558 52, 560179, 560187, 562581, 562583, C07F 708, C07F 718
Patent
active
053548795
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention provides optically active compounds useful as starting materials for various medicaments and a method for production thereof. For example, in a large scale production of optically active HMG-CoA reductase inhibitors in a high yield, optically active carboxylic esters provided by the present invention are very important.
BACKGROUND ART
It is generally known that the above-mentioned type of optically active compounds are obtainable through optical resolution of racemate or an asymmetric synthetic route. Conventional routes require, however, some special reagents or enzymes, or sometimes cumbersome steps. Furthermore, only a few methods for optical resolution of this type of compounds can give high optical purity enough for practical use.
Therefore, obtaining compounds of high optical purity is extremely important for synthesizing various compounds e.g., medicaments.
DISCLOSURE OF THE INVENTION
The present invention provides a simple asymmetric synthetic route for compounds of high optical purity on a large scale which utilizes a stereoselective reaction employing inexpensive reagents.
Under the circumstances described above, after a great many research efforts, the present inventors have found a method for production of optically active compounds useful as intermediates.
Namely, the present invention provides a method for production of compounds of high optical purity which are represented by Formula I: ##STR2## (wherein
R.sup.1 is hydrogen or a hydroxy protecting group;
R.sup.2 ' is hydrogen or optionally substituted lower alkyl;
Q is --CH.dbd.P(R.sup.3).sub.3 or --CHX'X
wherein aryl; optionally substituted lower alkoxy, optionally substituted aryl, or halogen;
X' is hydrogen or lower alkyl;
* is an asymmetric carbon).
Namely, the present method for production comprises converting a compound (II-(R)) or (II-(S)): ##STR3## (wherein R.sup.1 is the same as defined above), or ##STR4## (wherein R.sup.1 is the same as defined above), to a target compound of optically active carboxylate (I) by the following method (a) or (b).
Method (a)
(1) The compound (II-(R)) or (II-(S)) is subjected to a transesterification, namely, the compound is reacted with an optionally substituted alcohol such as methanol, ethanol, or the like, in the presence of a base catalyst such as sodium alkoxide, pyridine, or aluminum alkoxide, to give a compound (III-(R)) or (III-(S)): ##STR5## (wherein R.sup.1 is the same as defined above and R.sup.2 is optionally substituted lower alkyl), or ##STR6## (wherein R.sup.1 and R.sup.2 each is the same as defined above).
(2) Next, the free carboxylic acid is converted to acyl halide by a treatment with a halogenating agent (for example, phosphorus halide such as phosphorus trihalide, phosphorus pentahalide and the like, or thionyl halide), preferably in the presence of a basic material (e.g. an organic base such as pyridine), or converted to a mixed anhydride by treatment with haloformate (e.g. methyl chloroformate, ethyl chloroformate, iso-butyl chloroformate and the like) in the presence of a basic material (e.g. triethylamine and the like).
(3) Next, subjecting resultant to a reaction with phosphorus ylide: ##STR7## (wherein R.sup.3 R.sup.4 and R.sup.5 are respectively the same as defined above) and
if necessary, followed by a hydrolysis reaction, to give the target compound (Ia-(R)) or (Ia-(S)): ##STR8## (wherein R.sup.1, R.sup.2 ' and R.sup.3 are respectively the same as defined above), or ##STR9## (wherein R.sup.1, R.sup.2 ' and R.sup.3 are respectively the same as defined above).
Method (b)
The compound (II-(R)) or (II-(S)) is reacted with CH.sub.2 X'X (IVb): presence of a base in an organic solvent, and further, if necessary, followed by esterification, to give respectively the target compound (Ib-(S)) or (Ib-(R)): ##STR10## (wherein R.sup.1 R.sup.2 ', X, and X' each is the same as defined above), or ##STR11## (wherein R.sup.1 R.sup.2 ', X, and X' are respectively the same as defined above).
Namely, in method (a), the compound (Ia-(R))
REFERENCES:
patent: 3907852 (1975-09-01), Oswald et al.
Araki Yoshitaka
Konoike Toshiro
Shaver Paul F.
Shionogi Seiyaku Kabushiki Kaisha
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