反应详情

In a variation of the method described by Yarovenko et al, (Bull. Acad. Sci. USSR, Div. Chem. Sci. 1991, 40, 1924) ZnCl2 (1 N in ether, 120 mL, 120 mmol) was added in a dropwise fashion over 15 min to a magnetically stirred solution of N-hydroxy-isobutyramidine (12.2 g, 120 mmol) and 4-hydroxy-piperidine-1-carbonitrile (12.6 g, 100 mmol) in ethyl acetate (500 mL). Precipitate formed immediately upon addition, and at a point the stirring bar became immobilized in the matrix, requiring the reaction to be manually shaken for the remainder of addition. After standing for 15 min, the supernatant was decanted and filtered, and the residue was rinsed twice with ether, furnishing a hard white precipitate which was collected by filtration. This material was taken up in conc. HCl (50 mL), diluted to 4 N with EtOH (100 mL), and refluxed for 1 h. Upon cooling, a white precipitate was removed by filtration, then the filtrate was reduced to 50 mL and diluted with 100 mL water. Solid Na2CO3 was added until the mixture was basic, CH2Cl2 was added, and the resulting mixture was filtered, rinsing with CH2Cl2. The organic extract was separated, dried over MgSO4, and the solvent was removed to afford a viscous, amber oil as 1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-ol (15.0 g, 71% yield): 1H NMR (CDCl3) δ 3.95 (m, 3 H), 3.37 (m, 2 H), 2.88 (m, 1 H), 2.34 (br s, 1 H), 1.93 (m, 2 H), 1.63 (m, 2 H), 1.28 (d, 6 H, J=7.1 Hz), MS m/z 212.3 (M+).

1. customPrecipitate formed immediately upon addition
2. customthe reaction
3. customthe supernatant was decanted
4. filtrationfiltered
5. washthe residue was rinsed twice with ether
6. customfurnishing a hard white precipitate which
7. filtrationwas collected by filtration
8. additiondiluted to 4 N with EtOH (100 mL)
9. temperaturerefluxed for 1 h
10. temperatureUpon cooling
11. customa white precipitate was removed by filtration
12. additiondiluted with 100 mL water
13. additionSolid Na2CO3 was added until the mixture
14. additionCH2Cl2 was added
15. filtrationthe resulting mixture was filtered
16. washrinsing with CH2Cl2
17. extractionThe organic extract
18. customwas separated
19. dry with materialdried over MgSO4
20. customthe solvent was removed