Improved process for producing an optically active atenolol useful as a β-adrenergic blocker for the treatment of angina pectoris, arrhythmia and hypertension, which comprising reacting a phenol compound with an optically active epihalohydrin to give an intermediate, optically active glycidyl ether compound, followed by reacting the intermediate with isopropylamine, and purification method of the optically active atenolol in high yield by means of forming a salt of atenolol with a Bronsted's acid whereby the salt of optically active atenolol having high optical purity can be separated from the salt of racemic atenolol by solid-liquid separation method.

Process for producing optically active atenolol and intermediate thereof

PROBLEM TO BE SOLVED: To provide a method for safely preparing a glycidoxy-dihydrobenzopyran derivative with a high purity by a simple and easy operation SOLUTION: The preparation method includes a process for yielding the glycidoxy-dihydrobenzopyran derivative by reacting a hydroxy-dihydrobenzopyran derivative with an epihalohydrin in the presence of a base The quantity of the epihalohydrin consumed is set at 20-40 mol per mol of the hydroxy-dihydrobenzopyran, and the reaction is conducted in a mixed solvent consisting of water and a water-soluble organic solvent, eg acetone, having a relative permittivity of 10-23 COPYRIGHT: (C)2007,JPO&INPIT

Preparation method of dihydrobenzopyran derivative

PROBLEM TO BE SOLVED: To provide a method for simply obtaining high-purity nipradilol in which two kinds of racemic isomers exist in nearly the same ratio. SOLUTION: The method for producing nipradilol [3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy-3-nitroxy-2H-1-benzopyran] comprises reacting a crude substance of 3,4-dihydro-8-(2,3-epoxy)propoxy-3-nitroxy-2H-1-benzopyran obtained by reacting 3,4-dihydro-8-hydroxy-3-nitroxy-2H-1-benzopyran with an epihalohydrin with isopropylamine to provide a crude substance of nipradilol and selectively extracting the resultant nipradilol as a salt into a water phase and finally returning the salt to nipradilol. COPYRIGHT: (C)2007,JPO&INPIT

Method for producing dihydrobenzopyran compound

This invention relates to a method for producing a glycidyl ether of general formula (I), wherein A is an optionally substituted aryl or heteroaryl group and the asterisked carbon atom represents an asymmetric carbon atom, comprising reacting an aryl alcohol of the general formula A-OH, wherein A is as defined above, with an epihalohydrin in the presence of a quaternary ammonium salt and, if necessary, treating the reaction product with a base. This method can afford the glycidyl ether of formula (I), which is useful as an intermediate of drugs, especially a β-blocker, in a simplified manner with a high optical purity.

Production of glycidyl ether

A process is provided for preparation of a glycidyl ether represented by the general formula ##STR1## wherein A represents an aryl group optionally having a substituent or a heteroaryl group optionally having a substituent, and the carbon atom marked with * is an asymmetric carbon, which comprises reacting an aryl alcohol represented by the general formula A--OH (I) wherein A is as defined above, with an epihalohydrin in the presence of a quaternary ammonium salt; and, if necessary, further treating the reaction product with a base. According to the present process, it is possible to prepare by simple procedures and in a high optical purity glycidyl ethers of the above formula (II) useful as an intermediate for preparation of medicines, particularly medicines having β-adrenoreceptor blocking action or the like.

Process for preparation of glycidyl ether

PURPOSE:To obtain the titled substance useful as pharmaceuticals, etc., easily, without producing by-products, by reacting an o-allylphenol acetyl ester with an epoxidizing agent and cyclizing the obtained specific compound in the presence of an alkali halide, etc. CONSTITUTION:The compound of formula I (R is H, lower alkyl, lower alkoxy, halogen or nitro; n is 1-3; plural R groups may be same or different; R is lower acyl) is used as a raw material, and is made to react in the presence of an alkali halide or a quaternary ammonium halide, in a solvent (preferably acetone, etc.) at 50-120 deg.C under refluxing, and if necessary the product is deacylated to obtain the compound of formula II (R is H or acyl). The amount of the alkali halide or quaternary ammonium halide is preferably 0.1-1 mol- equivalent.

Ota Tomio

Papers

Production of glycidyl ether

Process for preparation of glycidyl ether

Produciton of 3,4-dihydro-2h-1-benzopyran-3-ol derivative