H. Lundbeck A/s

Robert Dancer

Hans Petersen

Michael Harold Rock

Henrik Pedersen

Ole Nielsen

Jens Kristian Perregaard

Benny Bang-Andersen

Ivan Mikkelsen

Ken Liljegren

Helle Eliasen

Haleh Ahmadian

Rikke E Humble

Yasuyoshi Ueda

Kim Andersen

Carla De Faveri

Thomas Ruhland

Takashi Yoshida

Florian Anton Martin Huber

Toshihiro Takeda

Takahisa Kato

Lars Ole Lyngso

Troels Volsgaard Christensen

Shogo Yamamoto

Michael Bech Sommer

Klaus Peter B&oslash;ges&oslash;

Marco Villa

Mario Rottl&auml;nder

Naoki Taoka

Federico Sbrogi&ograve;

Brian Christiansen

Rikke Eva Humble

The present invention relates to a novel method for the preparation of diol intermediates having the formula (II) and/or the opposite enantiomer of an acylated diol having the formula (IV) useful for the preparation of escitalopram involving selective enzymatic acylation or deacylation. 

Method for the separation of intermediates which may be used for the preparation of escitalopram

This patent discloses a method for resolution of 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile as a racemic or non-racemic enantiomer mixture into its isolated enantiomers, said method comprising the step of fractionally crystallizing 4-[4-(dimethylamino)-1-(4&#x2032;-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile as a salt with the (+)-(S,S)- or (&#x2212;)-(R,R)-enantiomer of O,O&#x2032;-di-p-toluoyl-tartaric acid in a solvent system comprising 1-propanol, ethanol or acetonitrile.

Method for manufacture of escitalopram

The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100&#xb0; C., as well as a method for making such an orodispersible tablet.

Crystalline base of escitalopram and orodispersible tablets comprising escitalopram base

The present invention relates to the crystalline base of the well known antidepressant drug escitalopram, S-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzo-furancarbonitrile, formulations of said base, a process for the preparation of purified salts of escitalopram, such as the oxalate, using the base, the salts obtained by said process and formulations containing such salts, and a process for the preparation of purified escitalopram free base or salts of escitalopram, such as the oxalate, using the hydrobromide, the salts obtained by said process and formulations containing such salts. Finally the present invention relates to an orodispersible tablet having a hardness of at least 22 N and an oral-disintegration time of less than 120 s and comprising an active pharmaceutical ingredient adsorbed onto a water soluble filler wherein the active pharmaceutical ingredient has a melting point in the range of 40-100&#xb0; C., as well as a method for making such an orodispersible tablet.

In the following, citalopram diol means 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile, as free base and/or acid addition salt. The invention relates to a process for the preparation of racemic citalopram diol and/or R- or S-citalopram diol, comprising the separation of a non-racemic mixture of R- and S-citalopram diol with more than 50% of one of the enantiomers into a fraction being enriched with S- or R-citalopram diol and a fraction comprising RS-citalopram diol wherein the ratio of R-citalopram diol:S-citalopram diol is equal to 1:1 or closer to 1:1 than in the initial mixture. The method is characterized in that (i) RS-citalopram diol is precipitated from a solution of the initial non-racemic mixture, or R- or S-citalopram diol is dissolved into a solvent from the initial non-racemic mixture, leaving a residue of RS-citalopram diol, and in that (ii) the residue/precipitate formed is separated from the final solution phase, followed by optional steps of repetition, recrystallisation, purification, isolation and conversion between free base and salts. The invention also relates to a process for the preparation of RS-citalopram, S-citalopram or R-citalopram (all as free base and/or acid addition salt) comprising the method described above followed by ring closure.

[object Object]

The present invention relates to a new method of preparing gaboxadol (THIP), which is useful for treating sleep disorders. In particular a method of preparing THIP comprising reacting a compound of formula (8b) or a salt thereof with an acid, typically a mineral acid, to obtain THIP as an acid addition salt. The present invention also relates to several intermediates 

Method for manufacture of THIP

The invention relates to a process for the preparation of racemic citalopram free base or an acid addition salt thereof and/or R- or S-citalopram as the free base or an acid addition salt thereof by separation of a mixture of R- and S-citalopram with more than 50% of one of the enantiomers into a fraction consisting of racemic citalopram and/or a fraction of S-citalopram or R-citalopram characterized in that i) citalopram is precipitated from a solvent as the free base or as an acid addition salt thereof; ii) the precipitate formed is separated from the mother liquor; iia) if the precipitate is crystalline it is optionally recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iib) if the precipitate is not crystalline, steps i) and ii) are optionally repeated until a crystalline precipitate is obtained and the crystalline precipitate is recrystallised one or more times to form racemic citalopram, and then optionally converted into an acid addition salt thereof; iii) the mother liquor is optionally subjected to further purification and S-citalopram or R-citalopram is isolated from the mother liquor and optionally converted into an addition salt thereof.

Process for the preparation of racemic citalopram and/or S-or R-citalopram by separation of a mixture of R-and S-citalopram

A method for the preparation of citalopram comprising reaction of a compound of formula 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran with an oxidising agent to prepare citalopram.

Method for the preparation of citalopram

Indane or dihydroindole derivatives

Benzofuran derivatives, their preparation and use

Method for the preparation of pure citalopram

The present invention relates to substituted indane or dihydroindole compounds of Formula (I)

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Hvidovre, Denmark

Robert Dancer