5-Bromo-2-chloronicotinic acid synthesis

Yield:29241-65-4 99%

Reaction Conditions:

Stage #1:5-bromo-2-hydroxynicotinic acid with thionyl chloride in N,N-dimethyl-formamide at 70; for 4 h;
Stage #2: with water in N,N-dimethyl-formamide for 1 h;

Steps:

48.B 8-(4-Methoxy-phenyl)-6-methyl-3-(4-piperidin-1-yl-but-1-ynyl)-5,6,7,8-tetrahydro-[1,6]naphthyridine trifluoroacetic acid salt
Step B. 5-Bromo-2-chloro-nicotinic acid. A mixture of 5-bromo-2-hydroxy-nictonic acid (32.9 g, 0.151 mol), SOCl₂ (167 mL), and DMF (10.5 mL) was heated at 70° C. for 4 h. The mixture was concentrated, cooled to 0° C., and quenched slowly with H₂O to give an off-white precipitate. The precipitate was stirred in H₂O for 1 h, and then was collected by filtration and dried under vacuum to give the title compound (35.5 g, 99%). The product was carried on to the next step without purification, but alternatively may be recrystallized from hot H₂O. MS (ESI): mass calcd. for C₆H₃BrClNO₂, 234.90; m/z found, 236.2 [M+H]⁺. ¹H NMR (acetone-d₆): 8.66 (d, J=2.5, 1H), 8.43 (d, J=2.5, 1H).

References:

Carruthers, Nicholas I.;Keith, John M.;Letavic, Michael A.;Shah, Chandravadan R. US2006/287292, 2006, A1 Location in patent:Page/Page column 26

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