Process for preparing levomilnacipran

1. A process for preparing levomilnacipran ((1S,2R)-cis-milnacipran) of formula (I)

or a salt thereof, comprising resolution of cis-milnacipran with optically active phenylglycine or optically active N-Boc-phenylglycine.

2. A process for preparing levomilnacipran ((1S,2R)-cis-milnacipran) of formula (I) or salts thereof, comprising

(a) reacting racemic cis-milnacipran free base with an the optically active L-phenylglycine of formula (II)

wherein R is an amine protecting group selected from tert-butyloxycarbonyl (Boc), benzoyl and p-methoxybenzylcarbonyl, in a non-aqueous organic solvent, to give the salt of formula (III)

(b) reacting the salt of formula (III) obtained in step (b) with a base, in water, to release levomilnacipran of formula (I);

(c) isolating said levomilnacipran from the reaction mixture of step (b) and optionally purifying it and/or transforming it into a salt of said levomilnacipran.

3. The process according to claim 2 , wherein R is a BOC (tert-butyloxycarbonyl) group.

4. The process according to claim 2 , wherein said non-aqueous organic solvent is selected from alcohols, ketones and esters.

5. The process according to claim 4 , wherein said non-aqueous organic solvent is an alcohol.

6. The process according to claim 5 , wherein said alcohol is 2-propanol.

7. The process according to claim 2 ,

wherein step (a) is performed at a temperature from 60° C. to 80° C.

8. The process according to claim 2 , wherein a molar ratio of racemic cis-milnacipran to the compound of formula (II) is essentially equimolar.

9. The process according to claim 2 , wherein in step (c) levomilnacipran is transformed into levomilnacipran hydrochloride.

10. A compound of formula (III)

wherein R is an amine protecting group.

11. The compound according to claim 10 having the formula (III′)