2-Fluoropyridine → (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-1-(2-pyridinyl)-2-piperidinone

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Reaction Steps

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.

Provenance & Evidence