Process development and pilot plant synthesis of methyl 2-bromo-6-chlorobenzoate

Organic Process Research and Development

Volumn 9, Issue 6, 2005, Pages 764-767

  Hickey, Matthew R ^a   Allwein, Shawn P ^a   Nelson, Todd D ^a   Kress, Michael H ^a   Sudah, Osama S ^b   Moment, Aaron J ^b   Rodgers, Stephen D ^b   Kaba, Mahmoud ^b   Fernandez, Paul ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Chemical Engineering Research and Development   (United States)

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EID: 28944447393     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0501444     Document Type: Article

References (16)

1. (a) Cohen, J. B.; Raper, H. S. J. Chem. Soc. 1904, 85, 1262.
2. (b) Cohen, J. B.; Smithells, C. J. J. Chem. Soc. 1914, 105, 1907.
3. Mongin, F.; Schlosser, M. Tetrahedron Lett. 1997, 37, 1559.
4. Based on analytically pure standard.
5. (a) 2,6-Dichlorophenyllithium: Kress, T. H.; Leanna, M. R. Synthesis 1988, 803.
6. (b) 2,6-Dibromophenyllithium: Luliñski, S.; Serwatowski, J. J. Org. Chem. 2003, 68, 5384.
7. (c) Halophenyl Inflates: Wickham, P. P.; Reuter, K. H.; Senanayake, H. G.; Zalesky, M.; Scott, W. J. Tetrahedron Lett. 1993, 34, 7521.
8. Determined by reaction calorimetry.
9. (a) Thomas, J.; Canty, J. J. Pharm. Pharmacol. 1962, 14, 587.
10. (b) A survey of the literature suggests dominance of esterification of 2,6-dihalobenozic acids by alkylative procedures. An instance of Fisher esterification of difluoro-iodo benzoic acids has been reported in poor yields: Rausis, T.; Schlosser, M. Eur. J. Org. Chem. 2002, 3351.
11. Ono, N.; Yamada, T.; Saito, T.; Tanaka, K.; Kaji, A. Bull. Chem. Soc. Jpn. 1978, 51, 2401.
12. 2.
13. The batch was drummed at this point to obtain an accurate assay yield, for basis of the charges for the subsequent esterification.
14. Batch 2 gave the acid in 90% assay yield followed by a 95% assay yield of the esterification.
15. LCAP represents LC area percent; LCWP represents LC weight percent.
16. Determined by quantitative GC analysis.