反应详情

A mixture of 4-[1-(2-Azetidin-1-yl-ethyl)-4-bromo-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (8800.00 mg; 21.29 mmol; 1.00 eq.), 4-fluoro-3-methylphenylboronic acid (3932.91 mg; 25.55 mmol; 1.20 eq.) and Cs2CO3 (13872.97 mg; 42.58 mmol; 2.00 eq.) in doxane (80 ml) and water (8 ml) was purged by argon for 10 min, then Bis(tri-t-butylphosphine)palladium(0) (435.20 mg; 0.85 mmol; 0.04 eq.) was added under argon flow and purged by argon for 1 min. The resulting mixture was stirred at 50 C overnight. The reaction solution was diluted with ethyl acetate 250 ml, washed with brine-100 ml×2. The organic layer was dried and concentrated to afford the crude product which is purified by biotage Ki-Sil column to yield 4-[1-(2-azetidin-1-yl-ethyl)-4-(4-fluoro-3-methyl-phenyl)-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (9370.00 mg; 99% yield).

1. customwas purged by argon for 10 min
2. custompurged by argon for 1 min
3. additionThe reaction solution was diluted with ethyl acetate 250 ml
4. washwashed with brine-100 ml×2
5. customThe organic layer was dried
6. concentrationconcentrated
7. customto afford the crude product which
8. customis purified by biotage Ki-Sil column