Process for production of 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionate ester and intermediate for the process

Abstract

Disclosed is a production process using, as an intermediate, a 6-(halomethyl)-1,2-benzisooxazol-3(2H)-one derivative represented by the general formula: Wherein R<5> represents a methyl group substituted by at least one phenyl group which may be substituted, or an oxygenated heterocyclic ring which may be substituted; and X represents a halogen atom. The process is useful for the production of 3-[5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl]propionic acid, which is useful as an antirheumatic agent, in a high yield and in a safe and simple manner.

Description

technical field [0001] The present invention relates to 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-oxo-2-substituted-2,3-dihydro-1,2 Process for the preparation of -benzisoxazol-6-yl)methoxy]phenyl}propionate and its intermediates. Background technique [0002] 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]benzene Propionic acid (hereinafter referred to as T-5224) has an excellent antiarthritic effect and a bone fracture inhibitory effect, and in addition, it is very safe, has excellent pharmacokinetics and is valuable as an antirheumatic agent ( Non-Patent Document 1). T-5224 is substituted by 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-oxo-2-substituted-2,3-dihydro-1 , 2-benzisoxazol-6-yl)methoxy]phenyl}propionate (hereinafter referred to as T-5224 intermediate) deprotected to prepare (Patent Document 1). This T-5224 intermediate is prepared by making 6-(bromomethyl)-2-(methoxymethyl)-1,2-benzisoxazol-3(2H)-one ...

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