- Process for the preparation of 5-cyanophthalide starting from 5-carboxyphthalide
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A new process is clescribed for obtaining 5-cyanophthalide, which is an intermediate used for the synthesis of citalopram and its active enantiomer S(+) citalopram, both of which are known active ingredients commonly used for treating depression. The process starts from 5-carboxyphthalide which is converted into the corresponding acylochloride. The latter is reacted with hydroxylamine to give the corresponding hydroxamyl phthalide which is subsequently subjected to a dehydration reaction to give 5-cyanophthalide.
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Page/Page column 4-5
(2008/06/13)
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- Process for the preparation of citalopram
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Preparation of citalopram comprises the steps of: (a) converting the compound of Formula (I) to a compound of Formula (II), wherein R in Formula (I) represents a C2 to C5 alkylene group which may be substituted or unsubstituted, and R1 in the compounds of Formula (II) represents a carboxylic acid group or a salt or an ester thereof; and (b) converting the compound of Formula (II) to form citalopram or a pharmaceutically acceptable salt thereof, or a direct conversion of the compound of Formula (I) to citalopram
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- Process for the preparation of 5-Formylphthalide
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There is described a process for the preparation of 5-formylphthalide by hydrogenation of a halide of 5-carboxyphthalide, dissolved in a dipolar aprotic solvent, in the presence of a catalyst.Furthermore, the use of 5-formylphthalide in the preparation of citalopram is described.
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- Method for the preparation of citalopram
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The present invention relates to a method for the preparation of citalopram or any of its enantiomers and acid addition salts thereof comprising treatment of a compound of formula (IV), wherein X is O or S; R1-R2are each independently selected from hydrogen and C1-6alkyl, or R1and R2together form a C2-5alkylene chain thereby forming a spiro-ring; R3is selected from hydrogen and C1-6alkyl, R4is selected from hydrogen, C1-6alkyl, a carboxy group or a precursor group therefore, or R3and R4together form a C2-5alkylene chain thereby forming a spiro-ring, with a dehydration agent or alternatively where X is S, thermally cleavage of the thiazoline ring, or treatment in presence of a radical initiator, to form citalopram. The invention also relates to intermediates used in the new process for the preparation of citalopram, as well as citalopram prepared according to the new process.
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- Method for the preparation of 5-cyanophthalide
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A method for the preparation of 5-cyanophthalide in which 5-carboxyphthalide is converted to the corresponding amide of Formula (IV) in which R is hydrogen or C1-6 alkyl, which is then reacted with a dehydrating agent thereby obtaining 5-cyanophthalide. The conversion of 5-carboxyphthalide to the corresponding amide of Formula (IV) may be carried out via the corresponding C1-6 alkyl or phenyl ester or the acid chloride, which is converted to the amide of Formula (IV) by amidation with ammonia or a C1-6 alkylamine. By the process 5-cyanophthalide, an important intermediate used in the preparation of the antidepressant citalopram, is prepared in high yields by a convenient, cost effective procedure.
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