反应详情

Potassium tert-butoxide (68 g, 0.606 mol) was added to a suspension of (5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone (WO 9807722) (200 g, 0.606 mol) in 1,2-dimethoxyethane (700 ml), and the mixture heated under reflux for 1 hour. 2-Fluoropyridine (59 g, 0.606 mol) was then added and the mixture stirred under reflux for 1 hour. Additional potassium tert-butoxide (34 g, 0.303 mol) and 2-fluoropyridine (30 g, 0.303 mol) were added and the reaction mixture stirred under reflux for a further hour. The cooled mixture was partitioned with water (500 ml), and the aqueous layer then extracted with ethyl acetate (2×500 ml). The combined organic extracts were dried (MgSO4), and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (20:80 to 100:0) to afford the title compound as a clear gum, 129 g.

1. temperaturethe mixture heated
2. temperatureunder reflux for 1 hour
3. temperatureunder reflux for 1 hour
4. stirringthe reaction mixture stirred
5. temperatureunder reflux for a further hour
6. customThe cooled mixture was partitioned with water (500 ml)
7. extractionthe aqueous layer then extracted with ethyl acetate (2×500 ml)
8. dry with materialThe combined organic extracts were dried (MgSO4)
9. customevaporated under reduced pressure
10. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (20:80 to 100:0)