Profiling the formation of 2-chloro-N,N-dimethylamino trimethinium chloride salt, a key intermediate in the manufacturing process of Etoricoxib

Organic Process Research and Development

Volumn 9, Issue 2, 2005, Pages 141-148

  Palucki, Michael ^a   Lin, Zhihao ^a   Sun, Yongkui ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(CHLOROMETHYLENE)DIMETHYLAMMONIUM CHLORIDE; 2 CHLORO N,N DIMETHYLAMINOTRIMETHINIUM CHLORIDE; ACETIC ACID DERIVATIVE; CARBON DIOXIDE; CHLORIDE; CHLOROACETIC ACID; CHLOROACETYL CHLORIDE; ETORICOXIB; N,N DIMETHYLFORMAMIDE; PHOSPHORUS DERIVATIVE; PHOSPHORUS OXYCHLORIDE; REAGENT; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DOCUMENTATION; DRUG MANUFACTURE; INFRARED SPECTROSCOPY; MATERIALS; MONITORING; NEAR INFRARED SPECTROSCOPY; REACTION ANALYSIS;

EID: 17444367380     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op049802v     Document Type: Article

References (22)

1. Davies, I. W.; Marcoux, J.-F.; Wu, J.; Palucki, M.; Corley, E. G.; Robbins, M. A.; Tsou, N.; Ball, R. G.; Dormer, P.; Larsen, R. D.; Reider, P. J. J. Org. Chem. 2000, 65, 8415-8420.
2. Davies, I. W.; Marcoux, J.-F.; Corley, E. G.; Journet, M.; Cai, D.-W.; Palucki, M.; Wu, J.; Robbins, M. A.; Gerena, L.; Sidler, R.; Larsen, R. D.; Rossen, K.; Pye, P. J.; Ashok, M.; Sager, J.; Volante, S.; Tsuo, N.; Ball, R. G.; DiMichael, L.; Reider, P. J. J. Org. Chem. 2000, 65, 4571-4574.
3. Petrich, S. A.; Hicks, F. A.; Wilkinson, D. R.; Tarrant, J. G.; Bruno, S. M.; Vargas, M.; Hosein, K. N.; Gupton, J. T. Tetrahedron 1995, 51, 1575-1584.
4. Marcoux, J.-F.; Corley, E. G.; Rossen, K.; Pye, P.; Wu, J.; Robbins, M. A.; Davies, I. W.; Larsen, R. D.; Reider, P. J. Org. Lett. 2000, 2, 2339-2341.
5. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W. J. Org. Chem. 1990, 55, 4735-4740.
6. Davies, I. W.; Marcoux, J.-F.; Reider, P. J. Org. Lett. 2001, 3, 209-211.
7. Davies, I. W.; Marcoux, J.-F.; Kuethe, J. T.; Lankshear, M. D.; Taylor, J. D. O.; Tsou, N.; Dormer, P. G.; Hughes, D. L. J. Org. Chem. 2004, 69, 1298-1308.
8. Davies, I. W.; Tellers, D M.; Shultz, C. S.; Fleitz, F. J.; Cai, D.; Sun, Y. Org. Lett. 2002, 4, 2969-2972.
9. Ostercamp, D. L.; Dinh, Y.; Graff, D.; Wiles, S. J. Org, Chem. 2003, 68, 3099-3105.
10. Davies, I. W.; Marcoux, J.-F.; Kuethe, J. T.; Lankshear, M. D.; Taylor, J. D. O.; Tsou, N.; Dormer, P. G.; Hughes, D. L. J. Org. Chem. 2004, 69, 1298-1308
11. After the studies described in this paper, a reverse phase ion-pairing HPLC method was developed for analysis of CDT using a YMC Basic column and acetonitrile/4 mM heptane sulfonic acid sodium salt as mobile phase. See ref 13.
12. For an excellent discussion on Process Analytical Chemistry and Spectroscopy, see: Hassell, C. D.; Bowman, E. M. Appl. Spectrosc. 1998, 52, 18A-29A and references therein.
13. The general procedure has been published: Davies, I. W.; Marcoux, J.-F.; Taylor, J. Org. Synth. 2003, 80, 200. Caution! Phosphorous oxychloride is highly toxic and corrosive and reacts violently with water liberating HCl, phosphoric acid, and heat.
14. Martens, H.; Naes, T. Multivariate Calibration; John Wiley and Sons: August 1994; pp 116-125
15. (a) Arnold, Z. Collect. Czech. Chem. Commun. 1961, 26, 3051-3057.
16. (b) Arnold, Z. Coll. Czech. Chem. Commun. 1965, 30, 2125-2127.
17. (a) Vilsmeier, A.; Haack, A. Chem. Ber. 1927, 60, 119.
18. (b) Paquette, L. A.; Johnson, B. A.; Hinga, F. M. OSC 1973, 5, 215.
19. 3 in DMF affords the desired product.
20. The identity of the chemical species associated with the absorbances in Figure 1 were confirmed by IR of authentic samples.
21. 3 is known to afford the acid chloride derivative. See: Ansell, M. F. In The Chemistry of Acyl Halides; Patai, S., Ed. Interscience Pusblisher: New York, 1972; pp 35-69.
22. 1H NMR. Thus 20-25% of the product is lost during anion exchange