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

HRID 577808Notes

Reaction equation

HRID 577808 reaction equation
[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

Participants

6

Reactant 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×

Product 1

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-02a6d8b425144d9292a54d70c6e212cb
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

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