反应详情

温度

100 °C

4-Hydroxypiperidine-1-carbonitrile (3.0 g) and N-hydroxy-2-methylpropanimidamide (2.9 g) are dissolved in ethyl acetate (20 ml) and 1 M ZnCl2 in Et2O (29 ml) is added. A precipitate forms and the solvent is decanted off. Additional Et2O (20 ml) is added to wash the precipitate and is decanted off. EtOH (20 ml) is added followed by conc. HCl (7.5 ml) and the mixture is heated to 100° C. for 3.5 h. The mixture is concentrated, redissolved in H2O (5 ml) and made basic by addition of concentrated NaHCO3. The aqueous layer is extracted with dichloromethane (2×50 mL) and the organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by silica gel chromatography (0% to 100% ethyl acetate/hexanes) to afford the title compound. LC (method 20): tR=1.56 min; Mass spectrum (APCI): m/z=212 [M+H]+.

1. customA precipitate forms and the solvent is decanted off
2. additionAdditional Et2O (20 ml) is added
3. washto wash the precipitate
4. customis decanted off
5. additionEtOH (20 ml) is added
6. concentrationThe mixture is concentrated
7. dissolutionredissolved in H2O (5 ml)
8. additionmade basic by addition of concentrated NaHCO3
9. extractionThe aqueous layer is extracted with dichloromethane (2×50 mL)
10. dry with materialthe organic layer is dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude product is purified by silica gel chromatography (0% to 100% ethyl acetate/hexanes)