反应详情

1-(4-Pyridyl)-4-piperidinemethanol (U.S. Pat. No. 4,968,704) (211.5 mg, 1.1 mmol), 5-chloro-N-(1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)-2-thiophenecarboxamide (306.7 mg, 1 mmol), triphenylphosphine (1049 mg, 4 mmol) are initially charged in 40 ml of THF, and diethylazodicarboxylate (DEAD) (696.6 mg, 4 mmol, 0.63 ml) is added. The mixture is stirred at room temperature overnight and then concentrated by evaporation, the residue is dissolved in ethanol, silica gel is added, the mixture is re-concentrated by evaporation and the residue is applied to a silica gel column. Elution with toluene/ethyl acetate and toluene/ethanol (25:1) mixtures gives a main fraction of Rf (SiO2, toluene/ethanol=4:1)=0.19. This fraction is evaporated and treated with ethanol, and the resulting crystals (112 mg, 23.3% of theory) are filtered off with suction. M.p.: 123° C. (decomp.).

1. concentrationconcentrated by evaporation
2. dissolutionthe residue is dissolved in ethanol
3. additionsilica gel is added
4. concentrationthe mixture is re-concentrated by evaporation
5. washElution with toluene/ethyl acetate and toluene/ethanol (25:1)
6. custommixtures gives a main fraction of Rf (SiO2, toluene/ethanol=4:1)=0.19
7. customThis fraction is evaporated
8. additiontreated with ethanol
9. filtrationthe resulting crystals (112 mg, 23.3% of theory) are filtered off with suction