4-Hydroxypiperidine-1-carbonitrile → 1-(3-Isopropyl-1,2,4-oxadiazol-5-YL)piperidin-4-OL

HRID 719466노트

반응식

HRID 719466 반응식
[OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[OH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]#N)[CH2:11][CH2:10]1>CCOCC.C(OCC)(=O)C.[Cl-].[Cl-].[Zn+2]>[CH:4]([C:3]1[N:7]=[C:15]([N:12]2[CH2:13][CH2:14][CH:9]([OH:8])[CH2:10][CH2:11]2)[O:1][N:2]=1)([CH3:6])[CH3:5]

참가 물질

6

반응물 2

HCID 218978254-Hydroxypiperidine-1-carbonitrileHCID 178449908HCID 178449908, 화합물

생성물 1

HCID 218977441-(3-Isopropyl-1,2,4-oxadiazol-5-YL)piperidin-4-OL수율 71%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매

실험 절차

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-hydroxypiperidine-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, 3H), 3.37 (m, 2H), 2.88 (m, 1H), 2.34 (br s, 1H), 1.93 (m, 2H), 1.63 (m, 2H), 1.28 (d, 6H, J=7.1 Hz); MS m/z 212.3 (M+).

후처리

  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

출처 및 근거

ORD 기록
ord-86ab5ca198e444f398ab99f998e4dbc6
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07132426B2

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