Sodium Hydroxide → 3-[1,1-Dimethyl-2-(tetrahydropyran-2-yloxy)-ethyl]-isoxazol-5-ylamine

HRID 1802403Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1802403
[CH3:1][C:2]([CH3:16])([CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1)[C:3](=O)[CH2:4][C:5]#[N:6].[OH-:17].[Na+].S(O)(O)(=O)=O.[NH2:24]O>O>[CH3:1][C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[O:17][N:24]=1)([CH3:16])[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1

Komponenten

5

Edukt 3

HCID 14798Sodium HydroxideHCID 159255Hydroxylamine, sulfate (1:1)HCID 592532944,4-Dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile

Produkt 1

HCID 592532173-[1,1-Dimethyl-2-(tetrahydropyran-2-yloxy)-ethyl]-isoxazol-5-ylamineAusbeute 117,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a stirred solution of 134 g (0.60 mol) of 4,4-dimethyl-3-oxo-5-(tetrahydro-pyran-2-yloxy)-pentanenitrile and 51.3 g (1.28 mol) of sodium hydroxide in water (1.3 L) are added 48.9 g (0.30 mol) of hydroxylamine sulfate. The reaction mixture is stirred at reflux for 18 h. After this time, the reaction mixture is cooled to room temperature and extracted with ethyl acetate (3×0.8 L). The organic layers are combined and washed with brine (1 L), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure. The residual brown oil is triturated with hexanes (0.8 L) while stifling and the resulting precipitate is isolated by filtration and dried in a vacuum oven for 2 d to yield 85 g of 3-[1,1-dimethyl-2-(tetrahydropyran-2-yloxy)-ethyl]-isoxazol-5-ylamine as a yellow solid. Yield 60%; m/z 241 [M+H], 157 [M+H—C5H8O]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18 (3H, s), 1.19 (3H, s), 1.45-1.75 (6H, m), 3.26 (1H, d, J=9.3 Hz), 3.4 (1H, m), 3.59 (1H, d, J=9.3 Hz), 3.68 (1H, m), 4.5 (1H, m), 4.88 (1H, s), 6.43 (2H, s).

Aufarbeitung

  1. temperatureat reflux for 18 h
  2. extractionextracted with ethyl acetate (3×0.8 L)
  3. washwashed with brine (1 L)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. customThe residual brown oil is triturated with hexanes (0.8 L)
  8. customthe resulting precipitate is isolated by filtration
  9. customdried in a vacuum oven for 2 d

Quellen und Nachweise

ORD-Eintrag
ord-913fee163a3645d8b03b9788fdc57c06
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08349871B2

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