Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2002-10-31
2004-02-03
O'Sullivan, Peter (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S355000, C564S357000, C564S358000
Reexamination Certificate
active
06686505
ABSTRACT:
RELATED APPLICATIONS
Foreign priority benefits are claimed under 35 U.S.C. §119(a)-(d) of Japanese patent application no. 2001-335322 filed on Oct. 31, 2001; and Japanese patent application no. 2002-251994 filed on Aug. 29, 2002.
FIELD TO WHICH THE INVENTION PERTAINS
The present invention relates to a process for producing an optically active amino alcohol from a nitro ketone or a cyano ketone with a high reaction yield and high optical purity, the optically active amino alcohol being useful as a synthetic intermediate for pharmaceuticals, agrochemicals, catalysts for asymmetric synthesis, etc., and also to a process for producing an optically active nitro alcohol or an optically active cyano alcohol, which are intermediates in the production of the optically active amino alcohol.
BACKGROUND OF THE INVENTION
Optically active &bgr;-amino alcohols are important compounds as synthetic intermediates for pharmaceuticals, agrochemicals, catalysts for asymmetric synthesis, etc., and with regard to the pharmaceuticals, for example, they are important as pharmaceutical intermediates for &bgr;-adrenergic blockers.
From the point of view of safety, efficacy, etc., it is extremely important for an optically active pharmaceutical to have high optical purity and there is therefore a strong desire for the establishment of a process for producing optically active bulk pharmaceuticals or intermediates with a high reaction yield as well as high optical purity.
With regard to conventional processes for producing optically active &bgr;-amino alcohols, there are known, for example, (1) a process in which an &agr;-azido ketone is asymmetrically reduced using bread yeast and the azido group of the &bgr;-azido alcohol thus obtained is reduced (J. S. Yadav, P. T. Reddy, S. Nanda, and A. B. Rao, Tetrahedron: Asymmetry, 12, 63 (2001)), (2) a process in which an &bgr;-amido ketone is asymmetrically reduced using a metal catalyst to give a &bgr;-amido alcohol, and aprotecting group on the nitrogen is removed (A. Kawamoto and M. Wills, Tetrahedron: Asymmetry, 11, 3257(2000)), and (3) a process in which an &bgr;-amino ketone is asymmetrically reduced using a metal catalyst (Comprehensive Asymmetric Catalysis, I. Springer, p. 210-212 (1999)).
Among the processes described above, process (1) has the defects that the type of reaction substrate is restricted and, moreover, the absolute configuration of the alcohol so obtained is limited to a specific type. In process (2), the yield when removing the protecting group on the nitrogen is low and it is not suitable for industrial production. Process (3) cannot always be said to have generality since the type of a suitable substrate depends on the type of a metal catalyst. Furthermore, the type of substituent on the nitrogen is restricted, and it lacks versatility.
On the other hand, there is no known process that can produce a &bgr;-amino alcohol by forming an optically active &bgr;-nitro alcohol derivative from an &agr;-nitro ketone by asymmetric reduction using a metal catalyst, and further reducing the intermediate thus obtained.
Optically active &ggr;-amino alcohols are important compounds as optically active pharmaceutical intermediates and are synthetic intermediates for, for example, fluoxetine, which is known as an antidepressant. There are various known processes for producing optically active &ggr;-amino alcohols. A process in which cinnamyl alcohol is subjected to Sharpless oxidation to give optically active 2,3-epoxycinnamyl alcohol, this is reduced with Red-Al to give the 1,3-diol, the 1-position is mesylated, and it is then reacted with an amine (Y. Gao and K. B. Sharpless, J. Org. Chem., 53, 4081 (1988)), and a process in which 3-chloropropiophenone is subjected to borane reduction in the presence of an optically active oxazaborolidine to give optically active 3-chloro-1-phenylpropanol, which is subsequently treated with sodium iodide and then reacted with an amine (E. J. Corey and G. A. Reichard, Tetrahedron Lett., 30, 5207 (1989)) have the problem that since large amounts of optically active material and reducing agent are required, the economic efficiency is poor, and the production cost is high.
In a process for obtaining an optically active &ggr;-amino alcohol by asymmetric hydrogenation of a &bgr;-amino ketone hydrochloride with MCCPM-Rh catalyst (S. Sakuraba and K. Achiwa, Synlett, 689 (1991)), there is the problem that the &ggr;-amino alcohol thus obtained has low optical purity. In a process in which an optically active &bgr;-cyano alcohol is obtained by a reaction between optically active styrene oxide and acetone cyanohydrin, and the cyano group is then reduced (D. Mitchell and T. M. Koenig, Synthetic Communications, 25, 1231 (1995)), since large amounts of optically active material and highly toxic compounds are required, it is not suitable for industrial production in terms of cost and safety. In a process in which a &bgr;-cyano alcohol racemate is synthesized by a reaction between benzaldehyde and acetonitrile, and the cyano group is further reduced to give a &ggr;-amino alcohol, which is then optically resolved to give an optically active &ggr;-amino alcohol(T. M. Koenig and D. Mitchell, Tetrahedron Lett., 35, 1339 (1994)), optical resolution, which is a very complicated operation, is required in order to obtain an optically active material, and there is also the defect that, since the starting material is used after optical resolution, half of the starting material is wasted.
With regard to a process for producing an optically active &bgr;-cyano alcohol by asymmetric reduction of benzoylacetonitrile, which is an &agr;-cyano ketone, there is a process in which the asymmetric reduction is carried out by a microorganism (J. R. Dehli and V. Gotor, Tetrahedron: Asymmetry, 11, 3693 (2000)). This process has the defects that the reaction yield is low and the absolute configuration of the alcohol so obtained is limited to a specific type.
With regard to the production of an optically active amino alcohol from a cyano ketone using a metal catalyst, a borane reduction process (using an optically active oxazaborolidine as a catalyst) is only disclosed in WO 00/07976, but this process has the problem of borane liquid waste since the borane compound and the cyano ketone are used in equimolar amounts.
With regard to a process for reducing a ketone to an alcohol using a transition metal complex, various techniques have been proposed. JP, A, 8-225466 discloses a hydrogen reduction process using an optically active phosphine and an optically active amine as ligands of a transition metal complex, and JP, A, 11-189600 relates to a process for producing an optically active alcohol from a carbonyl compound using a novel ruthenium complex having phosphine and amine ligands, etc. Furthermore, JP, A, 9-157196 and JP, A, 11-322649 disclose reactions of transition metal complexes having as a ligand an optically active nitrogen-containing compound using a hydrogen donor compound instead of hydrogen. JP, A, 9-157196 illustrates as reaction substrates a large number of carbonyl compounds having as one or more substituents an aromatic compound, a heterocyclic compound, an aliphatic compound, etc., and although they include carbonyl compounds substituted with a cyano group, which is electron-withdrawing and shows strong coordination to a transition metal, or a nitro group, which is electron-withdrawing, in the embodiments there is no mention of a reaction for their reduction into a cyano alcohol or a nitro alcohol using as a substrate a cyano ketone or a nitro ketone having a cyano or nitro group on the &agr;-carbon, and neither is there mention of other cyano ketones and nitro ketones.
Furthermore, WO 00/59885 discloses a process for producing a specific tricyclic amino alcohol derivative, etc. in which (R)-2-azido-1-(4-benzyloxy-3-methylsulfonyl amino)phenylethanol is synthesized by a hydrogen-transfer type asymmetric reduction of 2-azido-1-(4-benzyloxy-3-methylsulfonylamino)phenylethanone, but it cannot be predicted that &agr;-nitro ketones and &agr;-cyano keto
Ikariya Takao
Murata Kunihiko
Watanabe Masahito
Kanto Kaguku Kabushiki Kaisha
O'Sullivan Peter
Wolf Greenfield & Sacks P.C.
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