反应详情

To a stirred solution of 4-methylpyridin-2-amine (7.86 mmol, 850 mg) in THF (50 mL) was added dropwise a solution of 1M LiHMDS in THF (8.0 mmol, 8 mL) at room temperature. After the reaction mixture turned dark green, a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride (9.6 mmol, 2.56 g) in dichloromethane (55 mL) was added dropwise. The mixture was stirred at room temperature for 2.5 h and was then concentrated. 3% aq. Citric acid solution (18 mL) was added and the mixture was extracted with dichloromethane (2×15 mL). The combined organic layer was washed with 3% aq. citric acid solution, dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in THF (15 mL) and 6M NaOH solution (15 mL) was added. The mixture was stirred for 4 h. at room temperature. Ethyl acetate was added and the layers were separated. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography on silica (eluent: DCM/MeOH=98/2 to DCM/MeOH=95/5) to yield 1.1 g of N-(4-methylpyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (40.7%).

1. concentrationwas then concentrated
2. addition3% aq. Citric acid solution (18 mL) was added
3. extractionthe mixture was extracted with dichloromethane (2×15 mL)
4. washThe combined organic layer was washed with 3% aq. citric acid solution
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated
8. dissolutionThe residue was dissolved in THF (15 mL)
9. addition6M NaOH solution (15 mL) was added
10. stirringThe mixture was stirred for 4 h. at room temperature
11. additionEthyl acetate was added
12. customthe layers were separated
13. washThe organic layer was washed with water and brine
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. customevaporated
17. customThe residue was purified by chromatography on silica (eluent: DCM/MeOH=98/2 to DCM/MeOH=95/5)