Method for isolating (

1. A method of isolating (R)-tofisopam, substantially free of the (S)-enantiomer of tofisopam, said method comprising:

(a) adsorbing a mixture of enantiomers of tofisopam onto a chiral separation medium;

(b) passing a solvent system through the chiral separation medium in an amount sufficient to elute the tofisopam enantiomers from the separation medium;

(c) isolating the (R)-enantiomer of tofisopam, substantially free of the (S)-enantiomer of tofisopam;

wherein said chiral separation medium comprises:

(2S)-2-{(1S)[(3,5-dinitrophenyl)carbonylamino]phenylmethyl}-3,3-dimethylbutanoate covalently bound to silica, or

an amylose derivative of formula I:

wherein each R 1 is a radical of the formula II:

wherein R 2 and R 3 are independently selected from the group consisting of chloro and —CH 3 and are substituted on the radical of formula II in a substitution pattern selected from the group consisting of 3,4-dimethyl, 2,5-dimethyl, 3,4-dichloro, 2,5-dichloro, 5-chloro-2-methyl, 2-chloro-5-methyl, 4-chloro-3-methyl, 3-chloro-4-methyl, 3-chloro-2-methyl, 4-chloro-2-methyl, 2-chloro-6-methyl and 2-chloro-4-methyl; and

n is an integer from about 10 to about 100;

said amylose derivative coated on a porous inorganic carrier or a porous organic carrier.

2. The method of claim 1 wherein said separation medium comprises an amylose derivative of formula I.

3. The method of claim 2 wherein the substitution pattern on the radical of formula II is selected from the group consisting of 5-chloro-2-methyl and 3-chloro-4-methyl.

4. The method of claim 3 wherein said chiral separation medium comprises an amylose derivative of formula Ia:

wherein n is an integer from about 10 to about 100.

5. The method of claim 1 wherein said solvent system comprises acetonitrile.

6. The method of claim 5 wherein said solvent system further comprises an alkyl alcohol.

7. The method of claim 6 , wherein said alkyl alcohol is methanol.

8. The method of claim 7 , wherein said methanol is present in said solvent system in an amount of from about 5 to about 40 volume percent.

9. The method of claim 8 , wherein said methanol is present in said solvent system in an amount of from about 10 to about 35 volume percent.

10. The method of claim 9 , wherein said methanol is present in said solvent system in an amount of from about 15 to about 25 volume percent.

11. The method of claim 10 , wherein said methanol is present in said solvent system in an amount of about 19 volume percent.

12. The method of claim 1 wherein said chiral separation medium comprises (2S)-2-{(1S)[(3,5-dinitrophenyl)carbonylamino]-phenylmethyl}-3,3-dimethyl-butanoate covalently bound to silica.

13. The method of claim 12 wherein said solvent system comprises a mixture of heptane and an alkyl alcohol.

14. The method of claim 13 , wherein said alkyl alcohol is ethanol.

15. The method of claim 14 , wherein said ethanol is present in said solvent system in an amount of from about 25 to about 60 volume percent.

16. The method of claim 15 , wherein said ethanol is present in said solvent system in an amount of from about 35 to about 50 volume percent.

17. The method of claim 16 , wherein said ethanol is present in said solvent system in an amount of about 40 volume percent.

18. The method of claim 1 wherein the process is performed at a temperature of from about 5° C. to about 40° C.

19. The method of claim 18 wherein the process is performed at a temperature of about 25° C.

20. The method of claim 1 wherein said (R)-tofisopam is isolated in an enantiomeric excess of greater than 95%.

21. The method of claim 20 wherein said (R)-tofisopam is isolated in an enantiomeric excess of greater than 98%.

22. The method of claim 1 wherein the chiral separation medium is contained in a chromatography column.

23. A method of isolating the (R)-enantiomer of tofisopam, substantially free of the (S)-enantiomer of tofisopam, said method comprising:

(a) providing a chromatography column packed with a chiral separation medium comprising:

(2S)-2-{(1S)[(3,5-dinitrophenyl)carbonylamino]phenylmethyl}-3,3-dimethylbutanoate, covalently bound to silica through an alkylene ester linkage; or

an amylose derivative of formula I:

wherein each R 1 is a radical of the formula II:

wherein R 2 and R 3 are independently selected from the group consisting of chloro and —CH 3 and are substituted on the radical of formula II in a substitution pattern selected from the group consisting of 3,4-dimethyl, 2,5-dimethyl, 3,4-dichloro, 2,5-dichloro, 5-chloro-2-methyl, 2-chloro-5-methyl, 4-chloro-3-methyl, 3-chloro-4-methyl, 3-chloro-2-methyl, 4-chloro-2-methyl, 2-chloro-6-methyl and 2-chloro-4-methyl; and

n is an integer from about 10 to about 100;

said amylose derivative coated on a porous inorganic carrier or a porous organic carrier;

(b) providing a flow of a solvent system through said column;

(c) adsorbing a mixture of tofisopam enantiomers onto the chiral separation medium;

(d) passing a first amount of the solvent system through the chromatography column sufficient to elute from said chiral separation medium substantially all of the (S)-enantiomer of tofisopam present in the mixture of tofisopam enantiomers, substantially free of the (+) conformer of (R)-tofisopam; and

(e) passing a second amount of the solvent system through the chromatography column, sufficient to elute from the chiral separation medium the (+)-conformer of (R)-tofisopam substantially free of the (S)-enantiomer of tofisopam.

24. The method according to claim 23 wherein the chiral separation medium comprises an amylose derivative of formula I, and the solvent system comprises a mixture of acetonitrile and methanol.

25. The method according to claim 23 wherein the chiral separation medium comprises a (2S)-2-{(1S)[(3,5-dinitrophenyl)carbonylamino]-phenylmethyl}-3,3-dimethylbutanoate covalently bound to silica, and the solvent system comprises a mixture of heptane and ethanol.