Method for producing dibenzoxepin compound

Abstract

Disclosed is a method wherein (Z)-11-(3- dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2- acetic acid (general name: olopatadine) or an acid addition salt thereof, which is useful as a pharmaceutical product, is produced by processing a dibenzoxepin derivative represented by the formula [I] below with a dehydrating agent for obtaining a mixture of a dibenzoxepin derivative represented by the formula [II] below and a dibenzoxepin derivative represented by the formula [III] below, and then processing the thus-obtained mixture with an acid. In the formula [I], R1, R2 and R3 independently represent an alkyl group having 1-2 carbon atoms.) (In the formula [II], R1, R2 and R3 are as defined above.) (In the formula [III], R1, R2 and R3 are as defined above.

Description

technical field The present invention relates to a method for producing dibenzoxepin compounds useful as pharmaceuticals, and more specifically to (Z)-11-(3-dimethylaminopropylidene)-6,11-dihydrodibenzo [b, e] Production method of oxa-2-acetic acid. Background technique (Z)-11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenzo[b,e]oxa-2-acetic acid (common name: olopatadine) is the formula (IV ) compounds shown. This compound or its acid addition salt is known as a pharmaceutical compound useful as an antiallergic drug for allergic rhinitis, urticaria, etc. (Japanese Patent Publication No. 5-86925). In the chemical synthesis of olopatadine, the general Z-type olopatadine is produced simultaneously with the E-type isomer, so isomerization is necessary to efficiently obtain the target Z-type. In Japanese Patent Publication No. 5-86925 and Japanese Patent Publication No. 7-116174, it is described that when the target substance is obtained as a cis-trans mixture (EZ mixture),...

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Problems solved by technology

However, the above-mentioned isomerization method is not an effective method for obtaining the Z-type target

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