Réaction #78082

Équation de réaction

Bromine

6-hydroxynicotinic acid

→

6-hydroxy-5-bromonicotinic acid

Rendement 97.0%

Solvants

water

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONAfter the completion of the addition
2. 2
   Autrethe cooling bath was removed
3. 3
   workup.ADDITIONSaturated Na2SO5 was added slowly to the stirred mixture until the brown mixture
4. 4
   FiltrationThe solid was collected through filtration
5. 5
   Lavagewashed with water
6. 6
   Autredried under vacuum overnight

Mode opératoire

Bromine (4.2 mL, 81.4 mmol) was added dropwise to the suspension of 6-hydroxynicotinic acid Compound 116a (8.00 g, 57.6 mmol) in water (30 mL) at 4° C. After the completion of the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 4 h. Saturated Na2SO5 was added slowly to the stirred mixture until the brown mixture became white. The solid was collected through filtration, washed with water, and dried under vacuum overnight to give 12.17 g (97%) of 6-hydroxy-5-bromonicotinic acid as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ12.95 (brs, 1H), 12.55 (brs, 1H), 8.16 (s, 1H), 8.04 (s, 1H). Quinoline (1.0 mL, 8.47 mmol) was slowly added to the solution of POCl3 (2.0 mL, 21.5 mmol), followed by 6-hydroxy-5-bromonicotinic acid (3.92 g, 18.0 mmol) at room temperature. After heating at 120° C. for 2 h, the reaction was quenched by addition of water dropwise at 10° C. After the mixture was cooled at 4° C. for a few hours, the solid was collected through filtration, washed with water, and dried under vacuum overnight to give 3.68 g (87%) of Compound 116b as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ8.86 (s, 1H), 8.55 (s, 1H); MS (ES) m/z: 236 (M−H+).

Source