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

HRID 553617Notes

Reaction equation

HRID 553617 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

HCID 592532173-[1,1-Dimethyl-2-(tetrahydropyran-2-yloxy)-ethyl]-isoxazol-5-ylamineYield 117.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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 stirring 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-(tetrahydro-pyran-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).

Workup

  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. stirringwhile stirring
  9. customthe resulting precipitate is isolated by filtration
  10. customdried in a vacuum oven for 2 d

Sources & evidence

ORD record
ord-64128fbe70bc4263847308a4515c6d6d
Source dataset
uspto-grants-2011_11
Patent number
US08048899B2

Reaction notes

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