Abstract: The present invention relates to a method for synthesizing a pharmaceutically acceptable acid addition salt of (1S, 2R)-milnacipran comprising the following successive steps: (a) reaction of phenylacetonitrile and of (R)-epichlorhydrin in the presence of a base containing an alkaline metal, followed by a basic treatment, and then by an acid treatment in order to obtain a lactone; (b) reaction of said lactone with MNEt2, wherein M represents an alkaline metal, or with NHEt2 in the presence of a Lewis acid-amine complex, in order to obtain an amide-alcohol; (c) reaction of said amide-alcohol with thionyl chloride in order to obtain a chlorinated amide; (d) reaction of said chlorinated amide with a phthalimide salt in order to obtain a phthalimide derivative; (e) hydrolysis of the phthalimide group of said phthalimide derivative in order to obtain (1S, 2R)-milnacipran, and (f) salification of (1S, 2R)-milnacipran in a suitable solvent system in the presence of a pharmaceutically acceptable acid.

Abstract: The fluorinated derivatives of catharanthine according to the invention respond to the general formula I: in which: the dotted line expresses the possibility of the presence of a double bond when the substitution —X is absent or else a single bond when —X designates a substitution for a group: H, OR, NR?R?, SR, or a halogen atom with R, R? and R? designating independently of one another a hydrogen atom or a linear or branched alkyl group in C1 to C6, R1, R2 and R3 represent independently of one another an atom of hydrogen, of fluorine or a methylated group, on the condition nevertheless that at least one of the radicals R1 and R2 represents an atom of fluorine, and n=1 or 2.

Abstract: The present invention relates to a method for synthesizing a pharmaceutically acceptable acid addition salt of (1S, 2R)-milnacipran comprising the following successive steps: (a) reaction of phenylacetonitrile and of (R)-epichlorhydrin in the presence of a base containing an alkaline metal, followed by a basic treatment, and then by an acid treatment in order to obtain a lactone; (b) reaction of said lactone with MNEt2, wherein M represents an alkaline metal, or with NHEt2 in the presence of a Lewis acid-amine complex, in order to obtain an amide-alcohol; (c) reaction of said amide-alcohol with thionyl chloride in order to obtain a chlorinated amide; (d) reaction of said chlorinated amide with a phthalimide salt in order to obtain a phthalimide derivative; (e) hydrolysis of the phthalimide group of said phthalimide derivative in order to obtain (1S, 2R)-milnacipran, and (f) salification of (1S, 2R)-milnacipran in a suitable solvent system in the presence of a pharmaceutically acceptable acid.

Abstract: The fluorinated derivatives of catharanthine according to the invention respond to the general formula I: in which: the dotted line expresses the possibility of the presence of a double bond when the substitution —X is absent or else a single bond when —X designates a substitution for a group: H, OR, NR?R?, SR, or a halogen atom with R, R? and R? designating independently of one another a hydrogen atom or a linear or branched alkyl group in C1 to C6, R1, R2 and R3 represent independently of one another an atom of hydrogen, of fluorine or a methylated group, on the condition nevertheless that at least one of the radicals R1 and R2 represents an atom of fluorine, and n=1 or 2.