反应详情

温度

-78 °C

To a sol. of 4-[2-(tert-butyldimethylsilanyloxy)ethoxy]bromobenzene (WO 03/093267, 7.95 g, 24 mmol) in THF (200 mL) at −78° C. was added BuLi (1.6M in hexane, 17.12 mL, 27.4 mmol). The sol. was stirred at −78° C. for 30 min, then ZnCl2 (1M in THF, 30 mL, 30 mmol) was added. The resulting sol. was allowed to warm to rt, and 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957, 7.79 g, 20 mmol) in THF (20 mL) and Pd(PPh3)4 (0.69 g, 0.60 mmol) were added. The reaction mixture was heated to 50° C. for 1 h, and stirred 16 h at rt. The mixture was cooled to 0° C., and aq. sat. NH4Cl was added. EtOAc was added, and the org. phase was washed with brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 2:8→1:0) yielded the title compound (8.1 g, 82%). LC-MS: tR=1.23 min, ES+: 506.47.

1. temperatureto warm to rt
2. temperatureThe reaction mixture was heated to 50° C. for 1 h
3. stirringstirred 16 h at rt
4. temperatureThe mixture was cooled to 0° C.
5. washphase was washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customthe solvents were removed under reduced pressure
9. customPurification of the residue by FC (EtOAc/heptane 2:8→1:0)