Processes for preparing darifenacin hydrobromide

A process for preparing darifenacin hydrobromide comprising:

• a) combining 3-(S)-(+)-hydroxypyrrolidine, a solvent selected from the group consisting of a C6-9 aromatic hydrocarbon, a polar aprotic organic solvent, and mixtures thereof, a sulfonyl halide, and a base to obtain 1-X-sulfonyl-3-(S)-(−)-X-sulfonyloxypyrrolidine of formula I,
• b) reacting the 1-X-sulfonyl-3-(S)-(−)-X-sulfonyloxypyrrolidine of formula I with diphenylacetonitrile and an inorganic base in an organic solvent selected from the group consisting of a C6-9 aromatic hydrocarbon, a polar aprotic organic solvent, and mixtures thereof to obtain (S)-2,2-diphenyl-2-(1-X-sulfonyl-3-pyrrolidinil)acetonitrile of formula II;
• c) reacting the (S)-2,2-diphenyl-2-(1-X-sulfonyl-3-pyrrolidinil) acetonitrile intermediate of formula II with a bromine acceptor selected from the group consisting of phenol and naphthol and an acid to obtain (S)-2,2-diphenyl-2-(3-pyrrolidinil) acetonitrile salt of formula III,
• wherein the bromine acceptor is phenol only when the acid is HBr;
• d) combining the (S)-2,2-diphenyl-2-(3-pyrrolidinil) acetonitrile salt of formula III and an inorganic base with a solvent selected from the group consisting of water immiscible organic solvent, a polar aprotic organic solvent, water, and mixtures thereof to form a mixture;
• e) acidifying the mixture;
• f) heating the mixture
• g) basifying the mixture;
• h) combining the mixture with a C1-4 alcohol and L-tartaric acid to obtain 3-(S)-(+)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine tartrate of formula VI;
• i) converting 3-(S)-(+)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine tartrate of formula VI to Darifenacin hydrobromide.