反应详情

温度

140 °C

A mixture of (5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone (WO 9807722) (6.5 g, 19.7 mmol), potassium carbonate (3.05 g, 21.7 mmol), copper (I) iodide (400 mg, 2.1 mmol) and 2-bromo-6-methylpyridine (10.2 g, 60 mmol) in 1-methyl-2-pyrrolidinone (200 ml) was stirred at 140° C. for 24 hours. The cooled mixture was partitioned between ethyl acetate and 10% aqueous ammonia, and the layers separated. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with water, then brine (3×), dried (MgSO4) and evaporated under reduced pressure to give a gum. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 100:0) to afford the title compound as a brown solid, 3.02 g.

1. customThe cooled mixture was partitioned between ethyl acetate and 10% aqueous ammonia
2. customthe layers separated
3. extractionThe aqueous phase was extracted with ethyl acetate
4. washthe combined organic extracts were washed with water
5. dry with materialbrine (3×), dried (MgSO4)
6. customevaporated under reduced pressure
7. customto give a gum
8. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 100:0)