Ethyl Acetate → HCID 86282448, compound

HRID 1052968Notes

Reaction equation

HRID 1052968 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([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[OH:22].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([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[OH:22])=[C:5]([CH3:10])[O:4][N:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 5297654HCID 5297654, compound

Product 1

HCID 86282448HCID 86282448, compoundYield 49%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 3,5-dimethylisoxazol-4-ylboronic acid (120 g, 851 mmol, 2.0 eq), dichloro[1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) (10 g, 13.7 mmol, 0.03 eq), 5-bromo-3-(4-fluorophenyl)-3-hydroxyindolin-2-one (136 g, 422 mmol, 1.0 eq) and Na2CO3 (100 g, 943 mmol, 2.2 eq) were dissolved in dioxane/H2O (800 mL/200 mL), which was heated to reflux for 5 h under N2 atmosphere. After cooled to room temperature, IL EA was added, the mixture was filtered through a pad of celite, the filter was washed with brine (1 L×2), dried over Na2SO4, concentrated, which was purified by silical gel to give 70 g yellow solid (yield, 49%). 1H NMR (400 MHz, DMSO-d6): δH 10.56 (s, 1H), 7.31-7.33 (m, 2H), 6.93 (d, J=8.0 Hz, 1H), 4.27-4.35 (m, 4H), 2.35 (s, 3H), 2.18 (s, 3H). MS (ESI) m/e [M+1]+ 339.

Workup

  1. temperaturewhich was heated
  2. temperatureto reflux for 5 h under N2 atmosphere
  3. filtrationthe mixture was filtered through a pad of celite
  4. washthe filter was washed with brine (1 L×2)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customwhich was purified by silical gel

Sources & evidence

ORD record
ord-1281ef3c5f9a484baef54c389a38177c
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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