Development of highly efficient resolutions of racemic tramadol using mandelic acid

Organic Process Research and Development

Volumn 6, Issue 5, 2002, Pages 729-737

  Evans, Graham R ^a   Fernández, Paloma Díaz ^a   Henshilwood, James A ^a   Lloyd, Steve ^a   Nicklin, Chris ^a  

^a UCB PHARMA   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; MANDELIC ACID; MANNICH BASE; TARTARIC ACID; TRAMADOL;

ARTICLE; CHEMICAL REACTION; DIASTEREOISOMER; DRUG SYNTHESIS; ENANTIOMER; GRIGNARD REACTION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; THERMODYNAMICS;

EID: 0036747126     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0255276     Document Type: Article

References (22)

1. The biologically active isomer was developed by Grunenthal in the 1970s; here they describe this isomer as trans. Commercially, and within the patent literature, it is termed trans; however, under IUPAC terminology 1a and 1b would be classed as cis. To not confuse the issue, we have used trans nomenclature throughout for 1a and 1b. See: (a) Flick, K.; Frankus, E. U.S. Patent 3,652,589, March 28, 1972.
2. (b). Frankus, E.; Friedrichs, E.; Kim, S. M.; Osterloh, G. Arzneim.-Forsch./Drug Res. 1978, 28, 107.
3. (a) Frankus, E.; Friedrichs, E.; Kim, S. M.; Osterloh, G. Arzneim.-Forsch./Drug Res. 1978, 28, 114.
4. (b) Goeringer, K. E.; Logan, B. K.; Christian, G. D. J. Anal. Toxicol. 1997, 21, 529.
5. (a) Buschmann, W. W.; Graudums, I.; Jansen, P. U.S. Patent 5,723,668, March 3, 1998.
6. (b) Flick, K.; Frankus, E. U.S. Patent 3,830,934, August 20, 1974. See also: Newman, P. Optical Resolution Procedures for Chemical Compounds; Vol. 1, Amines and Related Compounds; Optical Resolution Information Center, Manhattan College, Riverdale: New York, 1981.
7. (b) Flick, K.; Frankus, E. U.S. Patent 3,830,934, August 20, 1974. See also: Newman, P. Optical Resolution Procedures for Chemical Compounds; Vol. 1, Amines and Related Compounds; Optical Resolution Information Center, Manhattan College, Riverdale: New York, 1981.
8. (c) Evans, G. R.; Henshilwood, J. A.; O'Rourke, J. Tetrahedron: Asymmetry 2001, 12, 1663 and Evans, G. R. World Pat. Appl. No. WO 00/32554, June 8, 2000.
9. (d) Itov, Z.; Meckler, H. Org. Process Res. Dev. 2000, 4, 291. For an earlier report on the use of this resolving agent, see: Elsing, B.; Blaschke, G. Arch. Pharm. (Weinheim, Ger.) 1991, 324, 719.
10. (d) Itov, Z.; Meckler, H. Org. Process Res. Dev. 2000, 4, 291. For an earlier report on the use of this resolving agent, see: Elsing, B.; Blaschke, G. Arch. Pharm. (Weinheim, Ger.) 1991, 324, 719.
11. (a) Forro, E.; Kanerva, L. T.; Fulop, F. Tetrahedron: Asymmetry 1998, 9, 513.
12. (b) Forro, E.; Fulop, F.; Kanerva, L. T. Magy. Kem. Foly. 1998, 104, 437.
13. (c) Cavoy, E.; Deltent, M. F.; Lehoucq, S.; Miggiano, D. J. Chromatogr., A 1997, 769, 49.
14. Gilbert, J. C.; Richards, A. J. M.; Bardsley, H. J. World Pat. Appl. No. WO 98/40053, September 17, 1998.
15. The efficiency factor S is used to indicate how effective a resolution is. When S = 1.0, the resolution is 100% efficient; see: Fogassy, E.; Faigl, F.; Darvas, F.; Acs, M.; Toke, L. Tetrahedron Lett. 1980, 21, 2841. In the case of tramadol DTTA typically provides a resolution with S ≥ 0.85.
16. Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates, and Resolutions, 2nd ed.; Krieger: Florida, 1994;, pp 299-301 and 382-383.
17. (a) Delepine, M.; Lareze, F. Bull. Soc. Chim. Fr. 1955, 104.
18. (b) Pope, W. J.; Read, J. J. Chem. Soc. 1910, 97, 988.
19. Cherkez, S.; Lerman, O.; Tennenbaum, M.; Avner, H.; Kunyevski, T. U.S Patent, 5,414,129, May 9, 1995.
20. Lerman, O.; Kaspi, J.; Brenner, D. U.S. Patent, 5,874,620, February 23, 1999.
21. Anderson, K. E., U.S. Patent, 5,877,351, March 2, 1999.
22. We were able to obtain an analytically pure sample of cis-tramadol hydrochloride from these liquors by repeated crystallisation from dichloromethane as described in ref 1a. This reference standard was required by the quality department, to help to ascertain the level of the cis isomers in the final product.