反应详情

(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.

1. temperatureThe reaction mixture was refluxed for 5 days
2. customafter which time the solvent was removed under reduced pressure
3. customthe residue partitioned between dichloromethane and water
4. customThe organic layer was separated
5. extractionthe product extracted with dichloromethane
6. dry with materialThe combined organic layers were dried over magnesium sulphate
7. customthe solvent removed under reduced pressure
8. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 95:5, by volume, chloroform