Acetohydroxamic Acid → {3-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzisoxazol-5-yl}methanol

HRID 245354

Reaktionsgleichung

Reaktionsgleichung von HRID 245354
[Si]([O:18][CH2:19][C:20]1[C:21]([N:30]2[CH2:35][C@H:34]([CH3:36])[O:33][C@H:32]([CH3:37])[CH2:31]2)=[C:22]([F:29])[C:23](F)=C([CH:27]=1)C#N)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[K+].[C:44]([NH:47][OH:48])(=O)[CH3:45].C[N:50](C=O)C>CCOC(C)=O>[NH2:50][C:44]1[C:45]2[CH:27]=[C:20]([CH2:19][OH:18])[C:21]([N:30]3[CH2:31][C@H:32]([CH3:37])[O:33][C@H:34]([CH3:36])[CH2:35]3)=[C:22]([F:29])[C:23]=2[O:48][N:47]=1

Komponenten

6

Edukt 4

HCID 1990Acetohydroxamic AcidHCID 6228DimethylformamideHCID 23665647Potassium tert-butoxideHCID 866580455-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorobenzonitrile2×

Produkt 1

HCID 67359017{3-amino-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-fluoro-1,2-benzisoxazol-5-yl}methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To an ice-bath cooled and stirred solution of 5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorobenzonitrile (Intermediate 6, 500 mg, 0.96 mmol) in DMF was added t-BuOK (161 mg, 1.4 mmol) followed by acetohydroxamic acid (108 mg, 1.4 mmol). The mixture was brought to room temperature and stirred for 12 hours. The reaction mixture was diluted with EtOAc and washed successively with 1 N HCl (1×250 mL), water and brine. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified over silica gel flash column using a gradient of ethyl acetate in pet. ether to give the title compound as a white solid. Yield: 200 mg, (70%).

Aufarbeitung

  1. temperatureTo an ice-bath cooled
  2. customwas brought to room temperature
  3. washwashed successively with 1 N HCl (1×250 mL), water and brine
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified over silica gel flash column

Quellen und Nachweise

ORD-Eintrag
ord-9150b07950a3457184f55072f551a817
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658641B2

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