反应详情

A solution of 1-(3,4-difluorobenzyl)-piperidin-4-ylamine (8.7 g; EP-A2-0625507) and triethylamine (7.0 ml) in dichloromethane (200 ml) stirring at ambient temperature was treated with 3-chlorocarbonyl-propionic acid methyl ester (5.2 ml). After stirring for 16 hours, the reaction mixture was washed with brine, the organic layer was dried (MgSO4), and evaporated to leave a white solid. This solid was suspended in ethanol (200 ml), treated with hydrazine hydrate (5 ml) and the resulting mixture was stirred at reflux for 16 hours and then allowed to cool. Water (30 ml) was added to the reaction mixture and the ethanol was evaporated. The aqueous residue was then extracted into dichloromethane (6×50 ml), the combined organics were dried (MgSO4) and evaporated to give the subtitle compound as a white solid. (4.8 g)

1. washthe reaction mixture was washed with brine
2. dry with materialthe organic layer was dried (MgSO4)
3. customevaporated
4. customto leave a white solid
5. stirringthe resulting mixture was stirred
6. temperatureat reflux for 16 hours
7. temperatureto cool
8. customthe ethanol was evaporated
9. extractionThe aqueous residue was then extracted into dichloromethane (6×50 ml)
10. dry with materialthe combined organics were dried (MgSO4)
11. customevaporated