Reaktion #78082

Reaktionsgleichung

Bromine

6-hydroxynicotinic acid

→

6-hydroxy-5-bromonicotinic acid

Ausbeute 97.0%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the completion of the addition
2. 2
   Sonstigethe 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
   Waschenwashed with water
6. 6
   Sonstigedried under vacuum overnight

Vorschrift

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+).

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