API CORPORATION

A method for producing a salicylic acid ester represented by general formula (2) below, in which salicylic acid and an alcohol represented by general formula (1) below are brought into contact with a solid acid catalyst at a reaction temperature of 50° C. to 200° C. X—R—OH  (1) (In the formula (1), R represents a linear or branched alkyl group having 1 to 6 carbon atoms. X represents a hydrogen atom or a hydroxyl group.) (In the formula (2), R and X are each as defined in the formula (1).)

A method for producing a compound represented by the formula (1): wherein LG is a leaving group, PG 1 is an amino-protecting group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), comprising reacting a compound represented by the formula (6): with an amino group protecting agent to obtain a compound represented by the formula (7): or a salt thereof; reacting the aforementioned compound represented by the formula (7) with a lactonization agent to obtain a compound represented by the formula (8): reacting the aforementioned compound represented by the formula (8) with an esterification agent to obtain a compound represented by the formula (9): and reacting the aforementioned compound represented by the formula (9) with a leaving group introduction agent.

A method for producing acetaminophen, the method comprising causing p-nitrophenol to undergo an acetamination reaction to produce the acetaminophen, by passing a solution containing the p-nitrophenol through a column packed with a catalyst while also passing an acetylating agent and hydrogen through the column. The catalyst is a supported metal catalyst in which a metal element is supported on a monolith porous body, and a reaction temperature of the acetamination reaction is 0° C. to 60° C., and a reaction pressure of the acetamination reaction is 0.1 MPa to 1 MPa.

High purity 2-naphthylacetonitrile with fewer impurities that is useful as a starting material or intermediate for the synthesis of various pharmaceutical products, agricultural chemicals, and chemical products, and a production method thereof. A high purity 2-naphthylacetonitrile having an HPLC purity of 2-naphthylacetonitrile of not less than 95 area %, and containing naphthalene compounds represented by the formulas (a)-(j) at a content of a predetermined area % or below. A method for producing high purity 2-naphthylacetonitrile.

A method of producing high-purity hydroxy-L-pipecolic acids that includes allowing an L-pipecolic acid hydroxylase, a microorganism or cell having the ability to produce the enzyme, a processed product of the microorganism or cell, and/or a culture liquid comprising the enzyme and obtained by culturing the microorganism or cell, to act on L-pipecolic acid as a substrate in the presence of 2-oxoglutaric acid and ferrous ion, wherein the L-pipecolic acid hydroxylase (1) acts on L-pipecolic acid in the presence of 2-oxoglutaric acid and ferrous ion to add a hydroxy group to the carbon atom at positions 3, 4, and/or 5 of L-pipecolic acid; and (2) has a catalytic efficiency (kcat/Km) with L-proline that is equal to or less than 7 times the catalytic efficiency (kcat/Km) with L-pipecolic acid.

Salicylic acid is produced with high productivity by reacting 2-halogenated benzoic acid in an aqueous solvent at a reaction temperature of 155° C. or higher and 300° C. or lower in the presence of a copper source and a ligand. Preferably, the method further includes a purification step A in which the obtained salicylic acid is brought into contact with a styrene-based synthetic adsorbent and/or a purification step B in which the obtained salicylic acid is brought into contact with zeolite. The compound is led to raw materials for various pharmaceuticals or intermediates thereof (for example, acetylsalicylic acid).

An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

The present invention provides a method for industrially producing a highly pure aromatic nitrile compound and a highly pure aromatic carboxylic acid compound safely and highly efficiently at low costs. Compound (2) is subjected to Willgerodt reaction in the presence of an additive as necessary, and the obtained amide compound (3) is hydrolyzed and neutralized to give carboxylic acid compound (4). Carboxylic acid compound (4) is reacted with a halogenating agent in the presence of a catalyst as necessary in an organic solvent, and further reacted with an amidating agent, and the obtained amide compound (5) or (6) is reacted with a dehydrating agent to give nitrile compound (1). Alternatively, carboxylic acid compound (4) is reacted with a halogenating agent and a compound represented by the formula R 6 SO 2 R 7 in the presence of a catalyst as necessary in an organic solvent to give nitrile compound (1). Np is a naphthyl group optionally having substituent(s), R 5 is an alkylene group having 1-3 carbon atoms, and other symbols are as described in the DESCRIPTION.

An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

The present invention provides high purity 2-naphthylacetonitrile with fewer impurities that is useful as a starting material or intermediate for the synthesis of various pharmaceutical products, agricultural chemicals, and chemical products, and a production method thereof. A high purity 2-naphthylacetonitrile having an HPLC purity of 2-naphthylacetonitrile of not less than 95 area %, and containing naphthalene compounds represented by the formulas (a)-(j) at a content of a predetermined area % or below. A method for producing high purity 2-naphthylacetonitrile, including the following step 1 and step 2: step 1: a step of subjecting 2′-acetonaphthone to a Willgerodt reaction in the presence of an additive where necessary, and hydrolyzing the obtained amide compound to give 2-naphthylacetic acid; step 2: a step of reacting the 2-naphthylacetic acid obtained in step 1, a halogenating agent and sulfamide in the presence of a catalyst as necessary in an organic solvent to give 2-naphthylacetonitrile.