Potassium Carbonate → (R)-4-(3-Fluoropyrrolidin-1-yl)-1-(5-methoxy-2-methyl-4-nitrophenyl)piperidine

Participants

Reaction Steps

8-(5-Methoxy-2-methyl-4-nitrophenyl)-1,4-dioxa-8-azaspiro[4.5]decane (INTERMEDIATE 16, 0.350 g, 1.14 mmol) and 4-toluenesulfonic acid hydrate (0.217 g, 1.14 mmol) in water (25 mL) were stirred under reflux for 6 h. The reaction mixture was allowed to cooled to RT and adjusted to pH 7 with potassium carbonate The mixture was concentrated in vacuo. The crude residue was taken up in EtOAc, washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. To the resultant crude 1-(5-methoxy-2-methyl-4-nitrophenyl)piperidin-4-one (0.30 g, 1.14 mmol) in acetonitrile (15 mL) was added (R)-3-fluoropyrrolidine hydrochloride (0.102 g, 1.14 mmol) and sodium triacetoxyborohydride (0.481 g, 2.27 mmol) and the reaction mixture was stirred at RT for 16 h. The mixture was concentrated in vacuo and the crude residue was taken up in EtOAc and washed with 10% aqueous sodium carbonate and brine. The organic layer was separated, dried over sodium sulfate and concentrated in vacuo to give the title product which was used in the next step without further purification (0.19 g, 50%). m/z 338.

Provenance & Evidence