反应详情

2.4 g (16.2 mmol) 3-(3-pyridyl)-acrylic acid and 2.3 ml (16.2 mmol) TEA are suspended in 50 ml abs. toluene and a solution of 1.5 ml (15.5 mmol) chloroformic acid ethyl ester in 20 ml abs. toluene are added dropwise under moisture exclusion and light cooling. This yellow suspension is stirred at RT for two hours and then a solution of 3.5 g (14.1 mmol) 3-(1-benzylpiperidin-4-yloxy)-propylamine in 20 ml abs. toluene is added dropwise. The mixture is stirred for two hours at RT and extracted by shaking three times in the heat, each with 10 ml water, 2 M sodium hydroxide and water again. The organic phase is concentrated under vacuum and the orange colored oily residue is chromatographically purified twice over silica gel with CHCl3/CH3OH/NH4OH (90/9/1 and 95/5/0 to 90/10/0) and crystallized from 10 ml acetic acid ethyl ester. Colorless crystals remain with a MP of 100–102° C.; yield: 1.9 g (35%).

1. temperaturecooling
2. stirringThe mixture is stirred for two hours at RT
3. extractionextracted
4. stirringby shaking three times in the heat
5. concentrationThe organic phase is concentrated under vacuum
6. customthe orange colored oily residue is chromatographically purified twice over silica gel with CHCl3/CH3OH/NH4OH (90/9/1 and 95/5/0 to 90/10/0)
7. customcrystallized from 10 ml acetic acid ethyl ester