Ethyl Acetate → 5-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one

HRID 1052960Notes

Reaction equation

HRID 1052960 reaction equation
[CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16](=[O:21])[C:15]2([OH:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Na+].[Na+].CC(=O)OCC>O1CCOCC1.O.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH3:1][C:2]1[C:6]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16](=[O:21])[C:15]3([OH:28])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[C:5]([CH3:10])[O:4][N:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 42569875-bromo-3-hydroxy-3-phenyl-1,3-dihydro-2H-indol-2-one

Product 1

HCID 862961015-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-oneYield 65.6%

Reagents, catalysts & solvents 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Under N2, a mixture of 3,5-dimethylisoxazol-4-ylboronic acid (28 g, 200 mmol, 1.5 eq), dichloro[1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) (4.5 g, 6.1 mmol, 0.05 eq), 5-bromo-3-hydroxy-3-phenylindolin-2-one (40 g, 132 mmol, 1.0 eq) and Na2CO3 (45 g, 425 mmol, 3.2 eq) in dioxane/H2O (500 mL/120 mL) was heated to reflux for 5 h. After cooled down, 500 mL EA was added, the mixture was filtered through a pad of celite, the filter was washed with brine (500 mL×2), dried over Na2SO4, concentrated, purified by sili-gel to give product 27.7 g (yield, 65.6%). 1H NMR (400 MHz, DMSO-d6): δH 10.51 (s, 1H), 7.25-7.34 (m, 6H), 7.10 (m, 1H), 6.99-7.01 (d, 1H, J=8.0 Hz), 6.72 (s, 1H), 2.33 (s, 31H), 2.16 (s, 3H). MS (ESI) m/e [M+1]+ 321.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 h
  3. temperatureAfter cooled down
  4. filtrationthe mixture was filtered through a pad of celite
  5. washthe filter was washed with brine (500 mL×2)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by sili-gel

Sources & evidence

ORD record
ord-1067096d611a4e0c87781b411c933dbe
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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