Sumika Fine Chemicals, Co.,ltd.

Sumitomo Chemical Company, Limited

Taiho Pharmaceutical Company Limited

Masami Igi

Tetsuya Ikemoto

Shigeya Yamazaki

Yoshihiro Kawada

Taro Ishibashi

Nobushige Itaya

Tadashi Katsura

Kiyoshi Sugi

Wei-Guo Gao

Yayoi Tagami

Teiji Yamaoka

Taketo Hayashi

Nobuhiro Arai

Hiroyuki Yumoto

Mitsuhiro Takeda

Taichi Yoshikawa

Mitsuyo Sugi

A compound of formula [V] is prepared by oxidizing a compound of formula [III]. Citalopram can be industrially and economically produced and at a high yield by converting a compound of formula [V], which is prepared from a compound of formula [III], to a compound of formula [VI], and then alkylating the compound of formula [VI] to form citalopram.

Production method of citalopram, intermediate therefor and production method of the intermediate

According to the present invention, citalopram hydrobromide dissolved in a solvent containing at least one member selected from the group consisting of alcohol having 1-3 carbon atoms, water and acetone is crystallized or recrystallized while controlling the cooling rate, thereby to 1) provide an industrial method for crystallizing citalopram hydrobromide, which enables easy control of the crystal characteristics, such as particle size, particle size distribution and aspect ratio and the like of the crystal, and 2) provide citalopram hydrobromide crystal having crystal characteristics useful as a pharmaceutical bulk.

Citalopram hydrobromide crystal and method for crystallization thereof

Citalopram can be industrially and economically produced and at a high yield by reacting a compound of the following formula [VI] with 3-(dimethylamino)propyl chloride in the presence of at least one of N,N,N',N&#x2032;-tetramethylethylenediamine and 1,3-dimethyl-2-imidazolidinone and a condensing agent. The compound of the following formula [III], which is a key compound for the production of citalopram, can be easily produced by subjecting the compound of the following formula [II] to reduction and cyclization.

Production method of an intermediate for citalopram

The present invention provides a production method of a compound of the formulawherein X is chlorine atom, bromine atom or iodine atom, as well as a production method of citalopram and intermediates therefor.

Production methods of citalopram and intermediates therefor

Process for preparing a piperidine derivative

The present invention relates to production of 2-cyclohexyl-2-hydroxy-2-phenylacetic acid useful as an intermediate for pharmaceutical products, by an industrial means, economically, safely in a good yield. Novel 2-(2&prime;-cyclohexen-1&prime;-yl)-2-hydroxy-2-phenylacetic acid ester obtained by reacting cyclohexene and benzoylformic acid ester in the presence of a Lewis acid is hydrolyzed and reduced to give 2-cyclohexyl-2-hydroxy-2-phenylacetic acid.

Production method of 2-cyclohexyl-2-hydroxy-2-phenylacetic acid intermediate therefor and production method thereof

Piperidine derivative and process for preparing the same

Citalopram can be industrially and economically produced and at a high yield by reacting a compound of the following formula &lsqb;VI&rsqb; with 3-(dimethylamino)propyl chloride in the presence of at least one of N,N,N&prime;,N&prime;-tetramethylethylenediamine and 1,3-dimethyl-2-imidazolidinone and a condensing agent.

Production methods of citalopram and an intermediate therefor

According to the method of the present invention, an alkali metal compound, dimethyl sulfoxide, trimethyloxosulfonium halide and 3-quinuclidinone are added in a specific order to give the following compound &lsqb;II&rsqb;. This compound is, without treatment or isolation, directly reacted with an alkali metal salt of phenothiazine to give the following compound &lsqb;III&rsqb;, from which the following compound &lsqb;I&rsqb; is obtained. During the production of compound &lsqb;I&rsqb;, a by-produced acidic gas is removed and water is added to ensure industrial, safe and efficient production of compound &lsqb;I&rsqb; at a constantly high yield. Inasmuch as the present invention enables production of the following highly pure compound &lsqb;A&rsqb; by eliminating hydrogen halide of compound &lsqb;I&rsqb; in glyme in the presence of at least one kind of a base selected from potassium hydroxide and potassium alkoxide, compound &lsqb;A&rsqb; having a high purity of not less than 85 mol % can be provided.

Highly pure phenothiazine compound, production method thereof, production method of intermediate therefor, and hydrate and novel crystal as starting materials for the intermediate

Citalopram can be industrially and economically produced and at a high yield by reacting a compound of the following formula &lsqb;VI&rsqb; with 3-(dimethylamino)propyl chloride in the presence of at least one of N,N,N&prime;,N&prime;-tetramethylethylenediamine and 1,3-dimethyl-2-imidazolidinone and a condensing agent. The compound of the following formula &lsqb;III&rsqb;, which is a key compound for the production of citalopram, can be easily produced by subjecting the compound of the following formula &lsqb;II&rsqb; to reduction and cyclization.

Production methods of 5-phthalancarbonitrile compound and an intermediate therefor

Production method of 5-phthalancarbonitrile compound, intermediate therefor and production method of the intermediate

An L-tartrate of a trans-(&minus;)-4-(4-fluorophenyl)-3-hydroxymethylpiperidine compound, represented by the formula (I):

L-tartrate of trans-(-)-4-(4-fluorophenyl)-3-hydroxymethylpiperidine compound and process for preparing the same

The present invention provides a production method of a 5-phthalancarbonitrile compound, which comprises the use of a novel compound of the formula &lsqb;I&rsqb;

Growing community of inventors

Osaka, Japan

Masami Igi