Process for the resolution of racemic (R,S) -5-(2-(2-(2- ethoxyphenoxy) ethylamino)propyl)-2-methoxybenzene sulfonamide (tamsulosin), its novel R and S isomers and their salts and processes for their preparation

A process for resolving a racemic mixture of (R) and (S) isomers of tamsulosin, said process comprising:

• (a) mixing a racemic mixture of tamsulosin or salts thereof and R(−)BPA in a medium comprising an organic solvent and optionally water to provide a first mixture;
• (b) maintaining the first mixture at a temperature from 20° to 60° C. for a period from 2 to 10 hours to provide a second mixture comprising solid S-tamsulosin-R-BPA salt;
• (c) filtering the second mixture to obtain the solid S-tamsulosin-R-BPA salt;
• (d) basifying the solid S-tamsulosin-R-BPA salt to provide a third mixture comprising S-tamsulosin free base;
• (e) recovering the solid S-tamsulosin free base from the third mixture by filtration and extraction with at least one organic solvent;
• and optionally
• (f) converting the S-tamsulosin free base to a pharmaceutically acceptable salt;
• (g) recovering the R-tamsulosin or a salt thereof from a filtrate obtained in step (c) above;
• and
• (h) recovering a chiral resolving agent-(R)-BPA used in the process from mother liquors obtained in steps (e) or (g).

An R,S-tamsulosin oxalate salt having at least one of the following properties:

• (a) an FT-infrared spectrum comprising characteristic peaks at wave numbers:
• 3408, 2983, 1591, 1332, 1154, 759, 597, 573 and 517 cm−1;
• (b) an x-ray diffraction spectrum comprising characteristic peaks of greater than 20% relative intensity at two theta values:
• 20.36, 22.33, 14.8 and 13.74;
• and
• (c) a differential scanning calorimetric graph comprising a single peak at 180.2° C.

A racemic tamsulosin salt selected from the group consisting of:

• (a) R,S-tamsulosin fumarate having a melting range of 200-202° C.;
• (b) R,S-tamsulosin maleate having a melting range of 155-159° C.;
• (c) R,S-tamsulosin salicylate having a melting range of 47-52° C.;
• and
• (d) R,S-tamsulosin tartrate having a melting range of 197-199° C.

A salt of R-tamsulosin-S-BPA having the following properties:

• (a) a specific optical rotation of [α]24D=+268±2° (C=0.35, methanol);
• (b) a differential scanning calorimetric graph with characteristic exotherm between 189° C. and 202° C., an endotherm between 221° C. and 227° C. and an exotherm between 285° and 320° C.;
• and
• (c) no peaks between 7 and 40 two theta values in an x-ray diffraction spectrum.

A salt of S-tamsulosin-R-BPA having the following properties:

• (a) a specific optical rotation of [α]24D=−270±2° (C=0.35, methanol);
• (b) a differential scanning calorimetric graph with characteristic exotherm between 200° C. and 219° C., an endotherm between 222° and 226° C. and an exotherm between 280° and 325° C.;
• and
• (c) no peaks between 7 and 40 two theta values in an x-ray diffraction spectrum.

A salt of R-tamsulosin having a chiral purity of greater than 99.8% by HPLC, wherein the salt is a member selected from the group consisting of:

• (a) R-tamsulosin oxalate having at least one of the following properties:
• (i) an x-ray diffraction spectrum comprising characteristic peaks of decreasing intensity at two theta values:
• 20.3, 21.7, 23.0, 15.6, 18.5, 12.4, 26.4, 17.9, 12.7 and 16.5;
• (ii) a melting range of 180-183.5° C.;
• and
• (iii) a differential scanning calorimetric graph comprising a split peak at 178.8-180.3° C.;
• (b) R-tamsulosin fumarate having at least one of the following properties:
• (i) an x-ray diffraction spectrum comprising characteristic peaks of decreasing intensity at two theta values:
• 22.4, 15.3, 25.8, 19.1, 20.7, 10.3, 22.8, 11.5, 21.0 and 12.3;
• (ii) a melting range of 191.6-194.2° C.;
• and
• (iii) a differential scanning calorimetric graph comprising a single peak at 192.5° C.;
• (c) R-tamsulosin maleate having at least one of the following properties:
• (i) an x-ray diffraction spectrum comprising characteristic peaks of decreasing intensity at two theta values:
• 15.3, 23.9, 21.4, 18.6, 19.6, 23.1, 14.6 and 22.8;
• (ii) a melting range of 128.4-131.3° C.;
• and
• (iii) a differential scanning calorimetric graph comprising a single peak between 113.3° C. and 120.9° C.;
• and
• (d) R-tamsulosin tartrate having at least one of the following properties:
• (i) an x-ray diffraction spectrum comprising characteristic peaks of decreasing intensity at two theta values:
• 14.9, 11.5, 22.2, 25.3, 20.4, 19.3, 22.9, 20.1, 25.9 and 10.2;
• (ii) a melting range of 179.5-182.7° C.;
• and
• (iii) a differential scanning calorimetric graph comprising a single peak between 179° C. and 180.7° C.

A process for preparing R-tamsulosin-S-BPA salt, said process comprising:

• (a) mixing a racemic mixture of tamsulosin or salts thereof and S(+)BPA in a medium comprising an organic solvent and optionally water to provide a first mixture;
• (b) maintaining the first mixture at a temperature from 20° to 60° C. for a period from 2 to 10 hours to provide a second mixture comprising solid R-tamsulosin-S-BPA salt;
• and
• (c) filtering the second mixture to obtain the solid R-tamsulosin-S-BPA salt.

A process for preparing S-tamsulosin-R-BPA salt, said process comprising:

• (a) mixing a racemic mixture of tamsulosin or salts thereof and R(−)BPA in a medium comprising an organic solvent and optionally water to provide a first mixture;
• (b) maintaining the first mixture at a temperature from 200 to 60° C. for a period from 2 to 10 hours to provide a second mixture comprising solid S-tamsulosin-R-BPA salt;
• and
• (c) filtering the second mixture to obtain the solid S-tamsulosin-R-BPA salt.