Water → HCID 22999709, compound

HRID 1935429Notes

Reaction equation

HRID 1935429 reaction equation
C([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12](I)=[C:11]([N:14]([S:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=2)(=[O:24])=[O:23])C(OCC(C)C)=O)[O:10][N:9]=1)(=O)C.[CH2:35]1[O:43][C:42]2[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][C:37]=2[O:36]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1>[O:36]1[C:37]2[CH:38]=[CH:39][C:40]([C:12]3[C:8]([O:7][CH2:6][CH2:5][OH:4])=[N:9][O:10][C:11]=3[NH:14][S:22]([C:25]3[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:32])[CH3:33])=[CH:27][CH:26]=3)(=[O:23])=[O:24])=[CH:41][C:42]=2[O:43][CH2:35]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2734371(2H-1,3-benzodioxol-5-yl)boronic acidHCID 22999712HCID 22999712, compound

Product 1

HCID 22999709HCID 22999709, compoundYield 42.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirring solution of 2-({5-[{[4-(tert-butyl)phenyl]sulfonyl}(isobutoxycarbonyl)amino]-4-iodo-3-isoxazolyl}oxy)ethyl Acetate (Preparation 5) (2.41 g) in dioxane (25 mL) was added 3,4-methylenedioxybenzeneboronic acid (0.72 g) followed by cesium carbonate (5.15 g) and water (3 mL). The reaction mixture was purged with nitrogen three times, after which time tetrakis(triphenylphosphine)-palladium(O) (140 mg). The reaction mixture was heated to reflux for about 2 hours. Ethanol (50 mL) and sodium hydroxide (2M, 50 mL) were added to the reaction mixture and then this was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the solid residue was partitioned between saturated ammonium chloride solution (100 mL) and ethyl acetate (100 mL). The organics were washed with brine (50 mL), dried over sodium, sulfate and concentrated under reduced pressure to yield the crude material as a brown oil. The crude material was purified by column chromatography (100 g silica) using a gradient elution of hexane (50% to 0%) and ethyl acetate (50% to 100%) and also with methanol (5% in ethyl acetate) to yield the product as a light brown foam (770 mg).

Workup

  1. customThe reaction mixture was purged with nitrogen three times
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for about 2 hours
  4. additionEthanol (50 mL) and sodium hydroxide (2M, 50 mL) were added to the reaction mixture
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe solid residue was partitioned between saturated ammonium chloride solution (100 mL) and ethyl acetate (100 mL)
  7. washThe organics were washed with brine (50 mL)
  8. dry with materialdried over sodium, sulfate
  9. concentrationconcentrated under reduced pressure
  10. customto yield the crude material as a brown oil
  11. customThe crude material was purified by column chromatography (100 g silica)
  12. washa gradient elution of hexane (50% to 0%) and ethyl acetate (50% to 100%)

Sources & evidence

ORD record
ord-f1d9e19e6cad4061978affab8066adc4
Source dataset
uspto-grants-2002_05
Patent number
US06387915B2

Reaction notes

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