Nippon Soda Co., Ltd.

Hirohito Oooka

Tsutomu Inoue

Masaya Akashi

Shinya Fukuhara

Takeshi Ohkuma

Noriyoshi Arai

Tsutomu Imagawa

Hiroki Inoue

Yasushi Shibata

Hiroshi Hakuta

A 9-azabicyclo[3.3.1]nonan-3-one derivative is reacted with a hydrogen in the presence of a catalyst composed of a ruthenium complex to obtain, at a low cost, an endo-9-azabicyclo[3.3.1]nonan-3-ol derivative useful as a production intermediate for agrochemical agents or medicines.

Method for producing endo-9-azabicyclo[3.3.1]nonan-3-ol derivative

A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(Px)[RRC*(NRR)-A-RRC*(NRR)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like). 

Production process of optically active 3-quinuclidinol derivative

There are provided, according to the present invention, a method for producing a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative, the method characterized in that a trans-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative or a mixture of the trans- and cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivatives is isomerized in the presence of an aluminum compound represented by a formula Al(OR)(wherein Rrepresents a hydrocarbon group in which a carbon atom having an oxygen atom bonded thereto is a secondary carbon atom). In the process, a ketone compound may be further added, in addition to the aluminum compound.

Method for producing cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative

The object is to produce an azabicycloalkanol derivative, particularly a cis-3-substituted-3-azabicyclo[3.2.1]octan-8-ol derivative which is a useful intermediate for agricultural chemicals or pharmaceutical agents, with a good yield and at an industrially low cost. A diastereomer of an azabicyclo-C-alkanol derivative having a methyne substituted a hydroxyl group as an asymmetric carbon (e.g., a trans-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative) is isomerized in the presence of a transition metal complex, thereby producing an excess amount of a thermodynamically more stable one of diastereomers (e.g., a cis-3-substituted-3-azabicyclo[3.2.1]-8-ol derivative). In this manner, a thermodynamically more stable one of diastereomers of the azabicyclo-C-alkanol derivatives can be produced.

Process for production of azabicycloalkanol derivative

Provided is a method for producing a piperidin-4-one derivative useful as an intermediate for agricultural chemicals or pharmaceutical products. A piperidin-4-one derivative represented by formula (III-a) or formula (III-b) is produced by reacting a cyclic bis(aminol)ether compound represented by formula (I) and an acetone derivative represented by formula (II) in the presence of at least one substance selected from the group consisting of protonic acids, Lewis acids, acid halides and dialkyl sulfuric acids.

Growing community of inventors

Hadano, Japan

Hirohito Oooka