Reacción #331404

Ecuación de reacción

1,4-dioxane

4-Bromo-7-chloro-8-fluoro-2-phenylquinoline

methane boronic acid

potassium carbonate

→

title compound

7-Chloro-8-fluoro-4-methyl-2-phenylquinoline

Disolventes

ethyl acetate

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato cool
2. 2
   OtroThe layers were separated
3. 3
   Extracciónthe aqueous layer extracted with ethyl acetate (30 mL)
4. 4
   Secadodried over sodium carbonate
5. 5
   Concentraciónconcentrated in vacuo
6. 6
   OtroThe residue was chromatographed on silica gel
7. 7
   Lavadoeluting with hexanes:methylene chloride 2:1

Procedimiento

4-Bromo-7-chloro-8-fluoro-2-phenylquinoline (1.1 g, 03.3 mmol), methane boronic acid (196 mg, 3.27 mmol), potassium carbonate (1.4 g, 9.8 mmol) and 1,4-dioxane (4 mL) were combined and stirred in a 10 mL R.B. flask. The flask was subjected to 3 vacuum-argon cycles. Tetrakis(triphenylphosphine)palladium(0) (380 mg, 0.33 mmol) was added, and the reaction was again subjected to 3 vacuum argon-cycles. The reaction was heated at 108° C. (external temperature) for 27 h, at which point the reaction was allowed to cool, and was diluted with ethyl acetate (30 mL), and water (30 mL). The layers were separated, and the aqueous layer extracted with ethyl acetate (30 mL). The organics were combined, dried over sodium carbonate, and concentrated in vacuo. The residue was chromatographed on silica gel, eluting with hexanes:methylene chloride 2:1. This afforded the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 2.75 (s, 3H), 7.47-7.55 (m, 4H), 7.69-7.72 (dd, 1H, J=8.9 & 1.6 Hz), 7.77 (s, 1H), 8.18-8.21 (m, 2H); MS (APCI+): 272.07 (100) [MH+], 274.03 (30) [(M+2)H+]; HPLC tR=3.80 min (OpenLynx, nonpolar—5 min).

Fuente