反应详情

温度

0 °C

1-(4-Hydroxy-piperidin-1-yl)-ethanone (301 mg, 2.10 mmol) is dissolved in DMF (10 mL) and 60% sodium hydride in mineral oil (84 mg, 2.10 mmol) is added at 0° C. The mixture is stirred for 15 min at 0° C. and 3-bromo-5-bromomethyl-4-chloro-pyridine (300 mg, 1.05 mmol) is added at that temperature. Then the mixture is warmed up to room temperature and stirred for 1 hr. Saturated NH4Cl aqueous solution (15 mL) is added, along with water (50 mL) and EtOAc (50 mL). The mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (2×50 ml). The organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 112 mg of 1-[4-(5-bromo-4-chloro-pyridin-3-ylmethoxy)-piperidin-1-yl]-ethanone.

1. temperatureThen the mixture is warmed up to room temperature
2. stirringstirred for 1 hr
3. stirringThe mixture is stirred for 10 min
4. customthe aqueous layer is separated
5. extractionextracted with EtOAc (2×50 ml)
6. concentrationconcentrated
7. customto give the crude product
8. customPurification by flash column chromatography