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Synthesis 2002(4): 0528-0532
DOI: 10.1055/s-2002-20959
PAPER
© Georg Thieme Verlag Stuttgart · New York

An Improved Procedure for the Large Scale Preparation of 5-Bromo-2-Hydroxynicotinic Acid [5-Bromo-3-Carboxy-2(1H)-Pyridone]

Bruno Haché, Jean-Simon Duceppe, Pierre L. Beaulieu*
Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval (Québec), H7S 2G5, Canada
Fax: +1(450)6828434; e-Mail: pbeaulieu@lav.boehringer-ingelheim.com;
Further Information

Publication History

Received 11 September 2001
Publication Date:
28 July 2004 (online)

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Abstract

Bromination of 2-hydroxynicotinic acid is conveniently carried out on a large scale using sodium hypobromite generated from sodium bromide and commercial bleach solution. This procedure safely provides high yields of pure 5-bromo-2-hydroxynicotinic acid [5-bromo-3-carboxy-2(1H)-pyridone], without use of hazardous elemental bromine.

Key words

bromine - electrophilic aromatic substitution - pyridine - bromination - hypobromite - combinatorial chemistry

    References

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7

The reaction of elemental Br2 with NaOH solutions to produce NaOBr is highly exothermic, and requires careful temperature control to avoid thermal decomposition.

10

Product 1 is easily separated from unreacted starting material 2 during the acidic aqueous workup. On the other hand, separation of 1 from dibrominated material 3 requires several triturations and is much less efficient.