Potassium Carbonate → (3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinol

Participants

Reaction Steps

(3R)-3-hydroxypiperidine hydrochloride (0.188 g) was added to a solution of 4-(bromomethyl)-2-fluoropyridine (0.26 g) [see Porter et al, WO 9622978] and potassium carbonate (0.189 g) in acetonitrile (15 ml). The reaction mixture was refluxed for 5 days, after which time the solvent was removed under reduced pressure and the residue partitioned between dichloromethane and water. The organic layer was separated and the aqueous was adjusted to pH 12 and the product extracted with dichloromethane. The combined organic layers were dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 95:5, by volume, chloroform:methanol to afford (3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinol (0.255 g) as a pale yellow oil.

Provenance & Evidence