反应详情

温度

10 °C

To a solution of 2,6-dimethoxypyridine (0.211 g, 1.51 mmol) in dry THF (7 mL) at −78° C. under Ar was added n-BuLi (1.53 M in hexanes, 1.18 mL, 1.81 mmol) dropwise. After the addition, the mixture was stirred at 10° C. for 30 minutes and then it was re-cooled to −78° C. To this mixture was added a solution of (previously fused in vacuo) zinc bromide (0.407 g, 1.81 mmol) in THF (2 mL) and the reaction mixture was allowed to warm to ambient temperature. The resulting mixture was cannulated into a flame-dried flask containing 4-(1-bromo-1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (0.532 g, 1.51 mmol) and Pd(PPh3)4 under Ar. The vessel was sealed and the mixture was heated at 90° C. (oil bath temperature) for 4 h. The cooled mixture was then quenched with saturated NH4Cl and extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was then purified by flash chromatography (SiO2/CH2Cl2-hexane, 7:3) to afford the title compound (0.295 g, 48%) as a yellow gum:

1. additionAfter the addition
2. temperatureit was re-cooled to −78° C
3. additionTo this mixture was added a solution of (
4. temperatureto warm to ambient temperature
5. customThe resulting mixture was cannulated into a flame-dried flask
6. customThe vessel was sealed
7. temperaturethe mixture was heated at 90° C. (oil bath temperature) for 4 h
8. customThe cooled mixture was then quenched with saturated NH4Cl
9. extractionextracted with EtOAc
10. dry with materialThe organic phase was dried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated to dryness
13. customThe residue was then purified by flash chromatography (SiO2/CH2Cl2-hexane, 7:3)