Nissan Chemical Industries Limited

Yasutaka Takada

Hiroo Matsumoto

Masami Yasukawa

Yuji Yoshimura

Syuji Morikiyo

Mikio Suzuki

Yoshio Ohara

Takanori Shimizu

Yoshinobu Yanagawa

Michiaki Adachi

Hirohide Kitsuyama

Shiro Kawahara

Mariko Ishida

Shouichi Tateyama

Yasuhiro Umeda

Miyako Kamon

Shinya Naitou

Akihiro Yoshida

The object of the present invention is to provide a method for producing in high yield with high stereoselectivity an optically active 5-hydroxy-3-ketoester compound which is useful as an intermediate for a pharmaceutical. A novel method for producing an optically active 5-hydroxy-3-ketoester compound in which an asymmetric aldol reaction by use of 1,3-diene compound is carried out in the presence of an optically active binaphthol-titanium complex together with a substituted nitrogen-containing 5 or 6-membered aromatic heterocyclic compound to obtain an optically active 5-hydroxy-3-ketoester compound in high yield with high stereoselectivity; and a novel production intermediate having a crystalline form.

Method for producing optically active 5-hydroxy-3-ketoester

Crystal forms of (3R,4S)-7-hydroxymethyl-2,2,9-trimethyl-4-(phenethylamino)-3,4-dihydro-2H-pyrano[2,3-g]quinolin-3-ol that are excellent as a drug, and production methods thereof. Production methods include crystallizing (3R,4S)-7-hydroxymethyl-2,2,9-trimethyl-4-(phenethylamino)-3,4-dihydro-2H-pyrano[2,3-g]quinolin-3-ol from an acetate ester solvent, an aliphatic hydrocarbon solvent, a nitrile solvent, an aromatic hydrocarbon solvent, a ketone solvent or an ether solvent, and crystal forms obtained according to the methods.

Crystal form of tricyclic benzopyran compound and production method thereof

A process for producing a high purity 3,5-dihydroxy6-heptenoic acid derivative by controlling the content of impurities such as denatured substances, is provided. When a 3,5-dihydroxy-6-heptenoic acid derivative is produced by a process which comprises a step of contacting the 3,5-dihydroxy-6-heptenoic acid derivative of the formula (1) wherein R is a Calkyl group, with a Clower alcohol-containing solvent, an alcohol containing solvent having its content of an oxidizing substance lowered, is used to at most 0.05 molar equivalent to a 3,5-dihydroxy-6-heptenoic acid derivative, to suppress impurities contained in the 3,5-dihydroxy-6heptenoic acid derivative. 

Process for producing high purity 3,5-dihydroxy-6-heptenoic acid derivative

A method for producing an alkyl (3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6-heptenoate of the formula (1) (wherein R is a Calkyl group), which is an intermediate for a cholesterol-reducing agent (a HMG-CoA reductase inhibitor), etc. A solution containing a compound of the formula (1) is subjected to liquid chromatography treatment using silica gel as the packing material, to separate its epimers contained therein. 

Method for producing a 3,5-dihydroxy-6-heptenoate

A process for producing 2-cyclopropyl-4-(4-fluorophenyl)-quinoline-3-carbaldehyde, which entails oxidizing 2-cyclopropyl-4-(4-fluorophenyl)-3-hydroxymethylquinoline with a salt of a hypohalogenous acid in the presence of a quaternary ammonium salt.

Process for producing quinolinecarbaldehyde

The present invention relates a process for producing the quinoline derivative (3) via the nitrile compound (1) obtained by reacting the aldehyde compound represented by formula (2) with diethyl cyanomethylphosphonate and its intermediate (1).

Process for the preparation of quinoline derivative and intermediate therefor

Growing community of inventors

Funabashi, Japan

Yasutaka Takada