反应详情

To a solution of 4-hydroxypiperidine-1-carbonitrile (1 g, 7.93 mmol) and N-hydroxyisobutyrimidamide (0.972 g, 9.51 mmol) in ethyl acetate (40 mL) was added zinc chloride (1 M in Et2O, 9.5 mL, 9.5 mmol) dropwise at rt under argon. Precipitate formed immediately, and the reaction mixture was stirred at rt for 30 min. The solid was collected via filtering, rinsed several times with ether. The solid was dissolved in concentrated HCl (4 mL, 132 mmol), diluted with ethanol (8 mL), and refluxed for 1 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated to approximately half of the volume, and diluted with water (15 mL). The solution was basified with solid Na2CO3, followed by extraction with CH2Cl2 (3×30 mL). The combined organic layers were washed with saturated NaHCO3 (60 mL) and brine. It was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (hexanes-EtOAc gradient 0-50% EtOAc) to afford 1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-ol (0.59 g, 2.79 mmol, 35% yield) as a clear colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.29 (d, J=7.07 Hz, 6H) 1.55 (d, 1H) 1.60-1.70 (m, J=12.98, 8.61, 8.61, 4.17 Hz, 2H) 1.93-2.02 (m, 2H) 2.89 (spt, J=6.95 Hz, 1H) 3.38 (ddd, J=13.20, 9.03, 3.79 Hz, 2H) 3.88-4.04 (m, 3H). LCMS (m/z)=212 (M+H)+.

1. customPrecipitate formed immediately
2. customThe solid was collected
3. filtrationvia filtering
4. washrinsed several times with ether
5. temperaturerefluxed for 1 h
6. temperatureThe reaction mixture was cooled to rt
7. filtrationfiltered
8. concentrationThe filtrate was concentrated to approximately half of the volume
9. additiondiluted with water (15 mL)
10. extractionfollowed by extraction with CH2Cl2 (3×30 mL)
11. washThe combined organic layers were washed with saturated NaHCO3 (60 mL) and brine
12. dry with materialIt was dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue was purified by column chromatography (hexanes-EtOAc gradient 0-50% EtOAc)