反应详情

温度

120 °C

In a 50 mL 4-necked flask, 5-bromo-6-cyclobutoxynicotinic acid (1 g, 3.68 mmol, Eq: 1.00, preparation see Example 47) and cesium carbonate (3.59 g, 11.0 mmol, Eq: 3) were combined with toluene (25 mL) and water (2.8 mL) to give a colorless solution. The reaction mixture was 3× degassed and purged with argon before successively potassium 2-furantrifluoroborate (959 mg, 5.51 mmol, Eq: 1.5), palladium(II) acetate (41.3 mg, 184 μmol, Eq: 0.05) and butyldi-1-adamantylphosphine (198 mg, 551 μmol, Eq: 0.15) were added. The evacuating-purging cycle was repeated after each addition. The reaction mixture was then heated to 120° C. for 5 hours when TLC showed that the starting material had disappeared. Work up: The reaction mixture was cooled to RT, poured into 30 mL 1N HCl and extracted with AcOEt/THF 2:1 (4×50 mL). The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was then purified by triturating it with methanol to afford 713 mg of the title compound as yellow solid; MS (EI) 258.4 (M−H)−.

1. customto give a colorless solution
2. customdegassed
3. additionwere added
4. additionafter each addition
5. temperatureThe reaction mixture was cooled to RT
6. extractionextracted with AcOEt/THF 2:1 (4×50 mL)
7. washwashed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude material was then purified
11. customby triturating it with methanol