Process for the preparation of Escitalopram
The present invention relates to an improved process for the preparation of Escitalopram of the Formula (I), which comprises, isolation of Diol compound as an oxalate salt, resolution of Diol compound and cyclization of resolved compound of Formula (VII). The present invention provides a process to obtain pure Diol compound by preparing its Oxalate salt, which is useful for resolution of enantiomers.
1. A process for the preparation of Escitalopram of Formula I,
which comprises,
(i) reacting the diol compound (VI),
with oxalic acid in an organic solvent to get crystalline oxalate salt of (±)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile [(±)-Diol oxalate] (VIa),
(ii) isolating the crystalline Diol oxalate (VIa) by filtration and neutralizing the oxalate salt to get pure diol compound (VI),
(iii) separating the enantiomers from the pure Diol compound (VI) with an optically active acid precipitant to obtain (S)-(−)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (VII),
(iv) cyclizing the (S)-(−)-Diol (VII) in an organic solvent in the presence of sulfonyl halide and a base to produce Escitalopram (I).
2. The process as claimed in claim 1 , wherein the organic solvent used in step-(i) is selected from methanol, ethanol, isopropanol, n-butanol, isobutanol.
3. The process as claimed in claim 1 , wherein the neutralization in step-(ii) is carried out using inorganic base, selected from aqueous ammonia, aqueous sodium hydroxide or aqueous potassium hydroxide.
4. The process as claimed in claim- 1 , wherein the optically active precipitant is Di-p-toluoyl-D-tartaric acid.
5. The process as claimed in claim 1 , wherein the solvent is used for cyclization is selected from methylene chloride, toluene, cyclohexane, tetrahydrofuran, acetonitrile.
6. The process as claimed in claim 1 , wherein the sulfonyl halide used for cyclization step is methanesulfonyl chloride.
7. The process as claimed in claim 1 , wherein the base used in cyclization step is an organic or an inorganic base and preferably an organic base.
8. The process as claimed in claim 7 , the organic base is triethylamine.