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

HRID 553617ノート

反応式

HRID 553617 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-64128fbe70bc4263847308a4515c6d6d
出典データセット
uspto-grants-2011_11
特許番号
US08048899B2

反応ノート

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