PREPARATION OF RIVASTIGMINE AND ITS SALTS - Patent There are provided processes for making rivastigmine. In one embodiment, the process includes reacting S-(-)-[1-(3-hydroxyphenyl)ethyl]dimethylamine with N-ethyl-N-methyl carbamoyl chloride in the presence of an organic base to obtain a free base of rivastigmine. The process of claim 1, wherein S-(-)-[1-(3-hydroxyphenyl)ethyl]dimethylamine is prepared by:a) reacting 1-(3-methoxy-phenyl)-ethylamine with optically pure mandalic acid to form a salt;b) reacting the salt of step a) with formic acid and formaldehyde to obtain S-(-)-1-(3-methoxy-phenyl)-ethyl amine; andc) reacting S-(-)-1-(3-methoxy-phenyl)-ethyl amine with aqueous hydrobromic acid to afford S-(-)-[1-(3-hydroxyphenyl)ethyl]dimethylamine. As referred to here in the term "bulk density untapped" is the weight of the sample divided by its non-packed volume and the term "bulk density tapped" is the weight of the sample divided by its packed volume. The units of bulk density are grams (g) per cubic centimeter (cc) or grams per milliliter. A powder having low bulk density will be lightweight and have greater surface area. A powder with high density will be much more compact and dense, exist as harder particles and will result in a more flow able product compared to powder with low bulk density Rivastigmine tartrate prepared according to the present application has residual solvents such as acetone less than 700 ppm; ethyl acetate less than 200 ppm; toluene less than 100 ppm; and each of isopropyl alcohol, n-Heptane, dichloromethane, methyl isobutyl ketone, pyridine less than 20 ppm.
