反应详情

To a solution of tert-butyl({1-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-4-yl}methyl)carbamate (50.28 g, 153 mmol, step 1) in methanol was added 4N hydrogen chloride in dioxane (200 mL, 800 mmol) at room temperature. After 4 h, the volatile materials were removed by evaporation. The resulting amorphous was precipitated with diethyl ether/methanol (5:1). The precipitate was collected and added to the ice cooled 6N aqueous sodium hydroxide (200 mL) gradually. The mixture was extracted with dichloromethane/methanol (10:1, 500 mL×4). The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuo to give 24.90 g (99%) of the title compound as a pale brown amorphous.

1. customthe volatile materials were removed by evaporation
2. customThe resulting amorphous was precipitated with diethyl ether/methanol (5:1)
3. customThe precipitate was collected
4. additionadded to the ice
5. temperaturecooled 6N aqueous sodium hydroxide (200 mL) gradually
6. extractionThe mixture was extracted with dichloromethane/methanol (10:1, 500 mL×4)
7. washThe combined organic phase was washed with brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo