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.