Hydroxyamine hydrochloride → 3-(Isoquinolin-6-yl)isoxazol-5-amine

HRID 598836Notes

Reaction equation

HRID 598836 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11](=O)[CH2:12][C:13]#[N:14])=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C([O-])(=O)C.[Na+].Cl.[NH2:22][OH:23]>CCO.O.CCOC(C)=O>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[CH:12]=[C:13]([NH2:14])[O:23][N:22]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

7

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 579505683-(Isoquinolin-6-yl)-3-oxopropanenitrile

Product 1

HCID 579507323-(Isoquinolin-6-yl)isoxazol-5-amineYield 42%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(isoquinolin-6-yl)-3-oxopropanenitrile (2.1 g, 11 mmol) in 60 mL of EtOH was added sodium acetate (5.3 g, 64 mmol) and hydroxylamine hydrochloride (3.7 g, 54 mmol) in 60 mL of water. The mixture was heated to reflux. After 3 hours, the reaction mixture was cooled to room temperature and diluted with 300 mL of EtOAc. The mixture was transferred to a separatory funnel and washed three times with 50 mL of water and once with 50 mL of brine. The remaining liquid was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1 to 5% MeOH/CH2Cl2), affording 3-(isoquinolin-6-yl)isoxazol-5-amine (0.96 g, 42% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.35 (s, 1H), 8.56 (d, J=6.5 Hz, 1H), 8.36 (s, 1H), 8.19 (d, J=8.6 Hz, 1H), 8.04 (dd, J=1.4 Hz, 8.5 Hz, 1H), 7.91 (d, J=5.9 Hz, 1H), 6.92 (s, 2H), 5.60 (s, 1H).

Workup

  1. temperatureThe mixture was heated to reflux
  2. customThe mixture was transferred to a separatory funnel
  3. washwashed three times with 50 mL of water
  4. dry with materialThe remaining liquid was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (1 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-411d036f8e3f471688abef985ec985c5
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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