Improved large-scale preparation of 4-iodopicolinic acid

Synthetic Communications

Volumn 26, Issue 10, 1996, Pages 2017-2025

  Lohse, Olivier ^a  

^a Sandoz Pharma Ltd   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

4 IODOPICOLINIC ACID; ORGANOIODINE DERIVATIVE; PICOLINIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0029977432     PISSN: 00397911     EISSN: None     Source Type: Journal    
DOI: 10.1080/00397919608003557     Document Type: Article

References (13)

1. Cochennec, C., Rocca, P., Marsais, F., Godard, A., Quéguiner, G., Synthesis 1995, 321
2. Rocca, P., Cochennec, C., Marsais, F., Thomas-dit-Dumont, L., Mallet, M., Godard, A., Quéguiner, G., J. Org. Chem. 1993, 58, 7832
3. Guillier, F., Nivoliers, F., Godard, A., Marsais, F., Quéguiner, G., Siddiqui, M. A., Snieckus, V., J. Org. Chem. 1995, 60, 292
4. Epsztajn, J., Bieniek, A., Kowalska, J. A., Tetrahedron 1991, 47, 1697
5. Lewis, N. and Mitchell, M., Chem. Ind. 1991, 374
6. Meyer, H. and Graf, R., Chem. Ber. 1928, 61, 2202
7. Mosher, H. S. and Look, M., J. Org. Chem. 1955, 20, 283
8. 4 that isolation of the free ester was much more convenient and that it could be purified by distillation. Our synthesis is simpler because the ester hydrochloride salt is isolated and purified by crystallization and it does not need to be hydrolyzed before the halogen exchange reaction.
9. When the methanol was added to the toluene solution of the acid chloride, the mixture separated in two phases with an oily residue. Inverse addition allowed the formation of fine and soft crystals.
10. Graf, R., Chem. Ber. 1931, 64, 21
11. 2O.
12. 3. We found that the use of oxalyl chloride at 0 °C gave the same side reaction to a lower extent (15% chloro-derivative for the preparation of N,N-diisopropyl 4-iodopicolinamide; the compound was obtained pure after recrystallization in hexanes).
13. At that time, an aliquot of the solution was quenched with methanol and injected in GC. The chromatogram revealed the presence of the product (79%), methyl picolinate (8.4%) and by-products (10.6%).