Réaction #1594580

Équation de réaction

2-Chloro-5-fluoroquinolin-6-ol

Intermediate 16

2-Chloro-5-fluoroquinolin-6-ol

4-borono-3-chlorobenzoic acid

NaHCO3

→

final product

Rendement 15.7%

3-chloro-4-(5-fluoro-6-hydroxyquinolin-2-yl)benzoic acid

Rendement 15.7%

Solvants

dioxane water

Conditions de réaction

Traitement

1. 1
   AutreThe mixture was degassed three times by evacuation and argon filling
2. 2
   workup.ADDITIONThe reaction was diluted with 20 ml of water
3. 3
   Filtrationfiltered
4. 4
   FiltrationThe precipitate was filtered
5. 5
   Lavagewashed with water
6. 6
   Autredried
7. 7
   AutreThe crude was purified by column
8. 8
   Autreevaporated
9. 9
   Autreto obtain white solid
10. 10
    AutreThe solid was triturated with diisopropyl ether

Mode opératoire

2-Chloro-5-fluoroquinolin-6-ol (Intermediate 16, 1.0 mmol) and 4-borono-3-chlorobenzoic acid (1.1 mmol) were mixed with 5% (Ph3P)4Pd and 4.0 mmol of NaHCO3 in 20 ml 50% dioxane/water. The mixture was degassed three times by evacuation and argon filling and heated at 95° C. overnight. The reaction was diluted with 20 ml of water and filtered. The filtrate was acidified with 1N HCl to pH=4. The precipitate was filtered and washed with water, dried. The crude was purified by column using AcOH/MeOH/EtOAC (1/5/94) as solvent B and hexanes as solvent A with gradient 2 to 100%. The fractions with compound were pooled and evaporated to obtain white solid. The solid was triturated with diisopropyl ether. 50 mg of final product was obtained. 1H-NMR (DMSO-d6, 300 MHz, TMS): δ 10.55 (b, 1H), 8.47 (d, 1H), 8.01-8.03 (m, 2H), 7.79 (m, 3H), 7.56 (t, 1H). MS (ESI): m/z=316.3 [M−1]−.

Source