Process for the preparation of 5-carboxyphthalide

A process for the synthesis of citalopram, comprising a process for the synthesis of 5-carboxyphthalide that comprises adding 1,3,5-trioxane and terephthalic acid to fuming sulfuric acid having an SO3 content of at least 20% and heating the mixture to 120° C., and allowing the temperature of the mixture to increase by spontaneous exothermia up to 130-135° C.

A process for the synthesis of 5-carboxyphtalide which comprises adding 1,3,5-trioxane and terephthalic acid to fuming sulfuric acid containing at least 20% of SO3, heating the mixture at 130-135 ° C. and isolating the 5-carboxyphthalide thus obtained.

A process for producing citalopram comprising a process for producing 5-carboxyphthalide which comprises adding 1,3,5-trioxane and terephthalic acid to fuming sulfuric acid having an SO3 content of at least 20% and heating the mixture to a temperature of 120 to 145° C., wherein the 5-carboxyphthalide is isolated by diluting the mixture with glacial acetic acid, the adding water and neutralizing with an alkaline metal base, in which the process for producing the 5-carboxyphthalide is carried out in a non-pressurized reactor.

A process for producing citalopram comprising a process for producing 5-carboxyphthalide which comprises adding 1,3,5-trioxane and terephthalic acid to fuming sulfuric acid having an SO3 content of at least 25-30% and heating the mixture to a temperature of 130 to 135° C., wherein the 5-carboxyphthalide is isolated by diluting the mixture with glacial acetic acid, then adding water and neutralizing with an alkaline metal base, in which the process for producing the 5-carboxyphthalide is carried out in a non-pressurized reactor.