Patent ID: 8846763

Claim:
A method for treating central nervous system (CNS) disorders selected from the group consisting of epilepsy, Parkinson's disease, Alzheimer's disease, depression, restless legs syndrome, pain and migraine which comprises the step of administering to a patient in need thereof an effective amount of (S)-2-[4-(3-fluorobenzyloxy)benzylamino]propanamide, (Ia) its R-enantiomer (I′a), their racemic mixture (Ia, I′a) or a pharmaceutically acceptable salt thereof, and, optionally, one or more additional active agents, wherein safinamide (Ia), its R-enantiomer (I′a), their racemic mixture (Ia, I′a) or a pharmaceutically acceptable salt thereof has a content of the impurity (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide (IIa), its R-enantiomer (II'a), their racemic mixture (IIa, II'a), or a salt thereof with a pharmaceutically acceptable acid which is lower than 0.03% (by weight) and is obtained by a process characterized in that a Schiff base intermediate of formula (IIIa) its R-enantiomer or their racemic mixture (IIIa, III'a), (i) is obtained by an iminoalkylation reaction of 4-(3-fluorobenzyloxy)benzaldehyde with L-alaninamide or D-alaninamide or the racemic mixture thereof, without any addition of molecular sieves, in a solvent selected from (C 1 -C 5 ) lower alkanols at a temperature between 20° and 30° C. in an amount of such solvent with respect to the aldehyde which allows formation of a suspension of the Schiff base in a saturated solution of the Schiff base in the same solvent, and (ii) after completion of the iminoalkylation reaction, is submitted to a reduction reaction with a reducing agent selected from sodium borohydride and potassium borohydride in an organic solvent selected from one or more (C 1 -C 5 ) lower alkanols, optionally with water, wherein the ratio of the organic solvent to the Schiff base allows the formation and the presence during a substantial portion of the reduction reaction course of a suspension of the Schiff base into the saturated solution of the Schiff base in the same organic solvent and ranges from 0.5 L to 3.0 L per each mole of Schiff base, (iii) the process being further characterized in that the 4-(3-fluorobenzyloxy)benzaldehyde starting material employed for the preparation of the Schiff base intermediate (IIIa), (III'a), or their racemic mixture (IIIa, III'a) has a content of 3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)benzaldehyde impurity lower than 0.03% (by weight); whereby safinamide (Ia), its R-enantiomer (I′a) or their racemic mixture (Ia, I′a) is obtained in a free base form and, optionally, said free base form is converted in a salt thereof with a pharmaceutically acceptable acid.