Organic compounds -- part of the class 532-570 series – Organic compounds – Phosphorus esters
Reexamination Certificate
2002-04-22
2004-10-05
McKane, Jospeh K. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Phosphorus esters
Reexamination Certificate
active
06800778
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a production method of an optically active naphthalene derivative having a pharmacological action, particularly a steroid C
17,20
-lyase inhibitory activity, a reagent for optical resolution thereof and a production method of the reagent for optical resolution. More specifically, the present invention relates to a production method of naphthalene derivatives which comprises use of an optically active cyclic phosphorus compound as a reagent for optical resolution, a salt formed during the optical resolution, a novel optically active dioxaphosphorinan useful as a reagent for optical resolution, a reagent for optical resolution containing a novel optically active dioxaphosphorinan and a production method of the reagent for optical resolution.
BACKGROUND ART
Since chemically synthesized naphthalene derivatives represented by the formula (I) have an asymmetric carbon and have two kinds of optical isomers, there is a demand for a technique to selectively and efficiently prepare an optically active form thereof. For the production of an optically active amino compound, it is a general practice to use what is called a diastereomer salt method which comprises reacting an optically active acid compound with an amino compound (racemate) and separating the resulting salt mixture based on differences in the physical properties. For use of this method, various optically active acidic compounds have been developed and utilized as reagents for optical resolution (Separation Purification Technique Handbook, The Chemical Society of Japan, Maruzen, p. 459 (1993)).
Some of the optically active compounds represented by the formula (II) can be prepared according to the method described in JP-A-61-103886 and the like and are used for the optical resolution of amino acids, such as p-hydroxyphenyl glycine and phenylalanine, and amino compounds, such as 1-phenyl-2-paramethoxyphenyl-ethylamine and 1,2-di(4′-chlorophenyl)-1,2-diamino-ethane.
An optically active compound represented by the formula (III) can be produced according to the method described in JP-B-55-47013 and the like and is used as a reagent for the resolution of amino acids such as adrenaline, lysine, glutamic acid and the like, amphetamines, basic antibiotics such as lincomycin, tetracycline and the like, atropine, scopolamine, catecholamine, ephedrine, morphine, phenothiazines, perhexilin, prostaglandins and intermediates therefor, &agr;-p-ethoxyphenylamino-N-n-propyl-propionamide, &agr;,&agr;-diphenyl-&agr;-(2-piperidine)methanol, DOPA and many other amines.
Of the reagents for optical resolution of amino compounds, an optically active dioxaphosphorinan described in The Journal of Organic Chemistry, Vol. 50, p. 4508 (1985) and JP-A-61-103886 shows relatively high efficiency of optical resolution and can be derived easily. Therefore, it characteristically permits selection of a preferable one from various reagents for optical resolution.
As a production method of an optically active dioxaphosphorinan, a method comprising optical resolution of a racemate of dioxaphosphorinan is disclosed in the above-mentioned publications.
On the other hand, what is called an asymmetric synthetic method, wherein an optically active compound is directly produced without relying on optical resolution, is remarkably progressing in recent years. For synthesis of an optically active hydroxyester compound, for example, asymmetric hydrogenation using a ruthenium—2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (abbreviated as BINAP) complex (Journal of the American Chemical Society, Vol. 109, p. 5856 (1987), asymmetric hydrogenation using 1,2-bis(tert-butylmethylphosphino)ethane (abbreviated as BisP*) (Tetrahedron Letters, Vol. 40, p. 2577 (1999)), and asymmetric hydrogenation using 1,2-bis(trans-2,5-diisopropylphosphorano)ethane (abbreviated as i-Pr-BPE) (Journal of the American Chemical Society, Vol. 117, p. 4423 (1995)) are known.
While an optically active dioxaphosphorinan shows a relatively high resolution efficiency and versatility as a reagent for optical resolution, it is frequently found to be unsuitable for optical resolution of an intermediate for a pharmaceutical product having a complicated chemical structure.
According to a method disclosed for the synthesis of optically active dioxaphosphorinan, dioxaphosphorinan as a racemate is optically resolved by a diastereomer salt method. Therefore, its theoretical yield does not exceed 50%. Moreover, this method requires an optically active amine in an equivalent amount as a reagent for optical resolution, but the optically active amine is not necessarily easily available. Thus, this method is not economically advantageous.
DISCLOSURE OF THE INVENTION
The present invention provides a method for producing (R) or (S)-(I) having a high optical purity by efficient optical resolution of a mixture of optical isomers of a naphthalene derivative represented by the formula (I), a general-purpose reagent for optical resolution, which is superior in resolution efficiency, and a method for producing the resolution reagent in a high yield and in an industrially advantageous manner.
The present inventors have found that the above-mentioned objects can be achieved by converting optical isomers of a naphthalene derivative represented by the formula (I) in a mixture to diastereomer salts with an optically active acidic compound and separating the salts, and intensively investigated further to complete the present invention.
Accordingly, the present invention relates to
(1) a production method of an optically active form of a compound represented by the formula:
wherein R is a nitrogen-containing heterocyclic group optionally having substituents, R
1
is a hydrogen atom, a hydrocarbon group optionally having substituents, or a aromatic heteromonocyclic group optionally having substituents, R
2
is a hydrogen atom or a lower alkyl group optionally having substituents, * shows the position of an asymmetric carbon, R
3
, R
4
, R
5
, R
6
, R
7
, R
8
and R
9
are each independently a hydrogen atom, a hydrocarbon group optionally having substituents, a hydroxy group optionally having substituents, a thiol group optionally having substituents, an amino group optionally having substituents, an acyl group or a halogen atom, and R
7
may be bonded with R
6
or R
8
to form, together with a carbon atom on a naphthalene ring, a 5 or 6-membered ring containing an oxygen atom, or a salt thereof, which comprises reacting a mixture of optically active compounds of the naphthalene derivative represented by the formula (I) with an optically active form of a compound represented by the formula:
wherein ring A is a benzene ring optionally having substituents, R
10
and R
11
are the same or different and each is a hydrogen atom, a hydrocarbon group optionally having substituents or a halogen atom, or R
10
and R
11
in combination represent an alkylene group optionally having substituents, and * shows the position of an asymmetric carbon, or an optically active form of a compound represented by the formula:
wherein ring B and ring C are each an aromatic ring optionally having substituents, separating the resulting salt and isolating an optically active form,
(2) the production method according to the above-mentioned (1), wherein the nitrogen-containing heterocyclic group optionally having substituents, which is represented by R, is an imidazolyl group optionally having substituents, a thiazolyl group optionally having substituents, an oxazolyl group optionally having substituents or a pyridyl group optionally having substituents,
(3) the production method according to the above-mentioned (1), wherein the nitrogen-containing heterocyclic group optionally having substituents, which is represented by R, is a 4 or 5-imidazolyl group optionally having substituents or a 3 or 4-pyridyl group optionally having substituents,
(4) the production method according to the above-mentioned (1), wherein, when the nitrogen-containing heterocyclic group optionally having substi
Adachi Mari
Aoki Isao
Kawada Mitsuru
Taya Naohiro
Yamano Toru
Chao Mark
McKane Jospeh K.
Ramesh Elaine M.
Saeed Kamal
Takeda Chemical Industries Ltd.
LandOfFree
Process for producing optically active naphthalene... 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 producing optically active naphthalene..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing optically active naphthalene... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3295185